HUGO ID Detailed Result 11179

PMID	Match String	Actual String	Score	Flanking text	Edited by	Edit
8841988	SOD	SOD	1.4	We measured the antioxidant actions of superoxide dismutase (SOD), SOD glutathione peroxidase (GSH-Px), GSH-Px and cytochrome c oxidase (CO) CO
8841988	SOD	SOD	1.4	Total SOD activity in spinal cord transections from patients with sporadic ALS
8899665	SOD1	SOD1	1.2	the same patients was examined for superoxide dismutase 1 (SOD1) SOD1 mutations
8899665	SOD1	SOD1	1.2	The search for SOD1 mutations by linkage study and cycle sequencing proved negative
8899665	SOD1	SOD1	1.2	We did not find evidence for SOD1 mutations by either method of study
9044305	SOD	SOD	0.9	supports the concept that decreases in Cu Zn-superoxide dismutase (SOD) SOD activity causes apoptotic cell death in neuronal cells
9092140	SOD	SOD	1.4	SOD research is an important step for a better understanding of
9172131	SOD1	SOD1	2.9	major cellular antioxidant enzyme Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 in familial ALS subjects 3 has initiated an intense investigation
9172131	SOD1	SOD1	2.9	fewer than 20_amp_#37 of familial ALS cases map to the SOD1 gene
9462746	SOD	SOD	0.9	We report that treatment with the superoxide dismutase (SOD) SOD mimetic Manganese 5 10 15 20-tetrakis (4-benzoic 4-benzoic acid porphyrin
9620775	SOD1	SOD1	2.0	Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons
9620775	SOD1	SOD1	2.0	encoding the oxygen radical metabolizing enzyme CuZn superoxide dismutase (SOD1) SOD1 and loss of motorneurons in the brain and spinal cord
9620775	SOD1	SOD1	2.0	test this hypothesis we generated transgenic Drosophila which express human SOD1 specifically in adult motorneurons
9620775	SOD1	SOD1	2.0	We show that overexpression of a single gene SOD1 in a single cell type the motorneuron extends normal lifespan
9620775	SOD	SOD	1.7	These results show that SOD activity in motorneurons is an important factor in ageing and
9633809	ALS	ALS	2.2	disease onset and progression in a transgenic model of familial ALS
9633809	SOD1	SOD1	2.2	that highly over-express a mutated human CuZn superoxide dismutase (SOD1) SOD1 gene gly93-->ala TgN(SOD1-G93A)G1H TgN SOD1-G93A G1H line found in some
9633809	ALS	ALS	2.2	TgN SOD1-G93A G1H line found in some patients with familial ALS (FALS) FALS have been shown to develop motor neuron disease
9633809	SOD	SOD	2.2	The mutant Cu Zn SOD exhibits essentially normal SOD activity but also generates toxic oxygen
9633809	SOD	SOD	2.2	The mutant Cu Zn SOD exhibits essentially normal SOD activity but also generates toxic oxygen radicals as a result
9745361	SOD1	SOD1	1.4	gene encoding Cu 2 /Zn Zn 2 superoxide dismutase ( SOD1
9745361	SOD1	SOD1	1.4	Mice made transgenic for mutant SOD1 developed selective motoneurone pathology strongly resembling human ALS (Ref Ref
9745361	SOD1	SOD1-dependent	1.4	aetiology of sporadic forms may involve mechanisms similar to the SOD1-dependent defects of fALS (Ref Ref 55
9745361	SOD1	SOD1	1.4	Mutations in SOD1 not only reduce the capacity to detoxify superoxide but actually
9745361	SOD1	SOD1	1.4	Abnormalities of SOD1 may result in defective glutamate transport since transgenic mice expressing
9745361	SOD1	SOD1	1.4	in defective glutamate transport since transgenic mice expressing an ALS-linked SOD1 mutation show increased tyrosine nitration of glutamate transporters 43 and
9745361	SOD1	SOD1	1.4	a result of altered function of mutant superoxide dismutase (SOD1) SOD1
9856861	SOD1	SOD1	0.8	enzyme catalase and partially prevented with the antioxidant vitamin E SOD1 the enzyme that removes superoxide did not protect against iron(III)/ascorbate
10077670	SOD	SOD	3.2	(FALS)-associated FALS -associated mutant Cu/Zn Cu Zn superoxide dismutase-1 (SOD) SOD induces apoptosis of neuronal cells in culture associated with an
10077670	SOD	SOD	3.2	SOD recently has been shown to prevent calcineurin inactivation initiating the
10077670	SOD	SOD-induced	2.4	the present investigations examining the role of calcineurin in mutant SOD-induced cell death
10077670	SOD	SOD	3.2	Wild-type or mutant SOD was expressed in neuronal cells by infection with replication-deficient adenoviruses
10077670	SOD	SOD	3.2	PC12 cells overexpressing human wild-type SOD exhibited higher calcineurin activity than cells expressing FALS-related mutant SOD
10077670	SOD	SOD	3.2	SOD exhibited higher calcineurin activity than cells expressing FALS-related mutant SOD (SODV148G); SODV148G however cells expressing SODV148G had calcineurin activity equal
10077670	SOD	SOD	3.2	to mock-infected cells suggesting that cell death induced by mutant SOD was not related to a decrease in calcineurin activity
10077670	SOD	SOD-mediated	2.4	The importance of rotamase activity in mutant SOD-mediated apoptosis was supported by experiments showing that overexpressed wild-type cyclophilin
10077670	SOD	SOD	3.2	These data suggest that mutant SOD produces a greater need for rotamase and also highlights possible
10077670	SOD	SOD	3.2	preparation of adenoviruses (AdVs) AdVs expressing wild type or mutant SOD have been described previously ( 12
10077670	SOD	SOD	3.2	Expression of SOD and calcineurin A was analyzed by Western blot analysis as
10077670	SOD	SOD	3.2	A previously described method was followed for immunohistochemical detection of SOD ( 12
10077670	SOD	SOD	3.2	The effect of wild-type (WT) WT or FALS-linked mutant SOD gene expression on viability of cells was determined as reported
10077670	SOD	SOD	3.2	SOD Activity Assay
10077670	SOD	SOD	3.2	SOD activity was determined in triplicate by using a colorimetric assay
10077670	SOD	SOD	3.2	Overexpression of WT- and FALS-Associated Mutant SOD with Replication-Deficient Adenoviruses
10077670	SOD	SOD	3.2	SOD expression in PC12 cells was determined by Western blot analysis
10077670	SOD	SOD	3.2	Endogenous rodent SOD was present in both the mock-infected (Fig Fig 1 A
10077670	SOD	SOD	3.2	of slower electrophoretic mobility consistent with that expected for human SOD was present in extracts from cells infected with AdSODWT AdSODV148G
10077670	SOD	SOD	3.2	The human SOD level in cells expressing SODWT SODV148G and SODA4V was similar
10077670	SOD	SOD	3.2	cells expressing SODWT SODV148G and SODA4V was similar to endogenous SOD seen in mock cells (Fig Fig 1 A
10077670	SOD	SOD	3.2	Effect of Overexpression of Mutant SOD on Neural Cell Viability
10077670	SOD	SOD	3.2	We determined the effect of expression of WT and mutant SOD on differentiated PC12 cells a model system for postmitotic neurons
10077670	SOD	SOD	3.2	that the cells that died were the ones expressing mutant SOD and that these cells died by apoptosis ( 12
10077670	SOD	SOD	3.2	Effect of Overexpression of Mutant SOD on Calcineurin Activity
10077670	SOD	SOD	3.2	We examined the effects of WT and mutant SOD overexpression on calcineurin activity in differentiated PC12 cells
10077670	SOD	SOD	3.2	We next tested whether the effects of SOD overexpression on calcineurin activity were related to a change in
10077670	SOD	SOD	3.2	CsA and CsA Analogs on Cell Death Induced by Mutant SOD Expression or NGF Withdrawal
10077670	SOD	SOD	3.2	To assess the relationship between SOD expression calcineurin activity and cell death cells were treated with
10077670	SOD	SOD-induced	2.4	As previously noted these results indicate that mutant SOD-induced cell death is not related to calcineurin inhibition
10077670	SOD	SOD-induced	2.4	Both CsA and PKF 211_amp_#x02013 811 significantly enhanced the mutant SOD-induced death of hippocampal neurons (Fig Fig 4 A
10077670	SOD	SOD	3.2	studies suggested that CsA and its immunosuppressive analogs might enhance SOD mutant-induced cell death through its interference with rotamase activity
10077670	SOD	SOD	3.2	Table 1 shows that the baseline SOD activity was similar in mock SODWT- and SODV148G-expressing cells CsA
10077670	SOD	SOD	3.2	mock SODWT- and SODV148G-expressing cells CsA caused a decrease in SOD activity that was significantly (albeit albeit slightly more in SODWT-expressing
10077670	SOD	SOD	3.2	the mutant SOD-expressing cells had a slightly greater decrease in SOD activity than SODWT-expressing cells
10077670	SOD	SOD	3.2	Our interpretation of these studies is that human SOD/rodent SOD rodent SOD heterodimers that are formed in the transiently expressing
10077670	SOD	SOD	3.2	interpretation of these studies is that human SOD/rodent SOD rodent SOD heterodimers that are formed in the transiently expressing cells may
10077670	SOD	SOD	3.2	In addition the mutant human SOD/rodent SOD rodent SOD heterodimers may be more sensitive to changes in
10077670	SOD	SOD	3.2	In addition the mutant human SOD/rodent SOD rodent SOD heterodimers may be more sensitive to changes in conformation than
10077670	SOD	SOD	3.2	sensitive to changes in conformation than the WT human SOD/rodent SOD rodent SOD heterodimers
10077670	SOD	SOD	3.2	changes in conformation than the WT human SOD/rodent SOD rodent SOD heterodimers
10077670	SOD	SOD	3.2	Effect of Overexpression of Cyclophilin A in SOD Mutant-Induced Cell Death
10077670	SOD	SOD-induced	2.4	further examine the role of cyclophilin rotamase activity on mutant SOD-induced cell death we transfected NGF-differentiated PC12 cells with wild-type CyPA
10077670	SOD	SOD-expression	2.4	CyPAWT produced _amp_#x0003e 50_amp_#x00025 protection from cell death after mutant SOD-expression compared with that seen with transfection of a control cDNA
10077670	SOD	SOD	3.2	5 B indicating that the apoptotic pathway induced by mutant SOD differs from that after growth factor removal
10077670	SOD	SOD-induced	2.4	investigate these issues we tested whether CyPA rescue of mutant SOD-induced cell death would be decreased with CsA treatment
10077670	SOD	SOD	3.2	FALS-associated mutant SOD is believed to kill neurons through a gain of adverse
10077670	SOD	SOD	3.2	We recently demonstrated that overexpression of mutant SOD leads to altered superoxide content and induces the death of
10077670	SOD	SOD	3.2	( 16 that WT SOD prevents calcineurin from inactivation
10077670	SOD	SOD	3.2	This finding suggested to us that mutant SOD might induce cell death because it fails to protect calcineurin
10077670	SOD	SOD-induced	2.4	in this death and to elucidate the mechanism underlying mutant SOD-induced cell death
10077670	SOD	SOD-induced	2.4	For the latter reason mutant SOD-induced cell death appeared unrelated to an effect on calcineurin activity
10077670	SOD	SOD-induced	2.4	To further investigate a role for calcineurin inactivation in mutant SOD-induced cell death we tested the effect of CsA a calcineurin
10077670	SOD	SOD-induced	2.4	demonstrate a lack of correlation between calcineurin activity and mutant SOD-induced cell death
10077670	SOD	SOD	3.2	Both NGF-withdrawal and expression of SOD mutations have been associated with the generation of O 2
10077670	SOD	SOD	3.2	hand CsA and its analogs enhanced death induced by mutant SOD
10077670	SOD	SOD	3.2	found that both drug classes enhanced apoptosis induced by mutant SOD indicating that the action of CsA may be related to
10077670	SOD	SOD	3.2	A role for rotamase in mutant SOD toxicity was supported by experiments comparing mutant SOD-induced cell death
10077670	SOD	SOD-induced	2.4	in mutant SOD toxicity was supported by experiments comparing mutant SOD-induced cell death after expression of CyPAWT vs an isomerase activity-deficient
10077670	SOD	SOD	3.2	the mutant CyPA protected cells from death induced by mutant SOD expression
10077670	SOD	SOD	3.2	importance of rotamase activity in modifying the effect of mutant SOD
10077670	SOD	SOD-induced	2.4	The findings that rotamase activity protects cells from mutant SOD-induced cell death and that there is roughly similar rotamase activity
10077670	SOD	SOD	3.2	WT- and mutant SOD-expressing cells suggests that cells expressing mutant SOD have a greater reliance on rotamase activity and has implications
10077670	SOD	SOD	3.2	Mutant SOD may increase the oxidative modification of proteins ( 30 and
10077670	SOD	SOD	3.2	especially sensitive to the free radical damage induced by mutant SOD because of their high oxidative activity at least partly resulting
10077670	SOD	SOD	3.2	also may have a role in the normal folding of SOD itself to help stabilize the enzyme or its dimers
10077670	SOD	SOD	3.2	This activity may be especially critical for abnormal FALS-associated mutant SOD function because SOD mutations may destabilize SOD or the dimer
10077670	SOD	SOD	3.2	be especially critical for abnormal FALS-associated mutant SOD function because SOD mutations may destabilize SOD or the dimer ( 3 37
10077670	SOD	SOD	3.2	abnormal FALS-associated mutant SOD function because SOD mutations may destabilize SOD or the dimer ( 3 37 and may lead to
10077670	SOD	SOD	3.2	We found that SOD activity decreased slightly more after mutant SOD expression than after
10077670	SOD	SOD	3.2	We found that SOD activity decreased slightly more after mutant SOD expression than after SODWT expression suggesting that the mutant enzyme
10077670	SOD	SOD	3.2	WT to the effects of CsA perhaps because the mutant SOD was more sensitive to a decline in rotamase activity and
10077670	SOD	SOD	3.2	may be that other proteins perhaps ones that interact with SOD are more sensitive to decreased rotamase activity
10077670	SOD	SOD	3.2	death seen after CsA treatment of PC12 cells expressing mutant SOD is related to its proapoptotic effect on these cells because
10077670	SOD	SOD	3.2	Figure 1 ( A Western blot analysis of SOD from PC12 cells 3 days after mock infection (lane lane
10077670	SOD	SOD	3.2	Table 1 Mean rotamase and SOD activity _amp_#x0005b percent of control (mock-infected) mock-infected PC12 Cells_amp_#x0005d
10077670	SOD	SOD	3.2	ALS amyotrophic lateral sclerosis SOD Cu/Zn Cu Zn superoxide dismutase-1 FALS familial ALS CyP cyclophilin
10077670	SOD	SOD	3.2	In 1993 mutations in Cu/Zn Cu Zn superoxide dismutase-1 (SOD) SOD were found to be associated with 20_amp_#x00025 of cases of
10077670	SOD	SOD-induced	2.4	investigations into the molecular mechanisms underlying the pathogenesis of mutant SOD-induced FALS
10077670	SOD	SOD	3.2	SOD is a ubiquitously expressed homodimeric cytosolic enzyme that dismutates superoxide
10077670	SOD	SOD	3.2	Mutant SOD has been hypothesized to cause FALS not through a loss
10077670	SOD	SOD	3.2	or an augmentation of a normally present nondismutase activity of SOD
10077670	SOD	SOD	3.2	transgenic mice ( 4 5 that suggest cells expressing mutant SOD do not necessarily have decreased dismutase function
10077670	SOD	SOD	3.2	In addition a SOD knockout mouse has normal motor neuron development ( 6 demonstrating
10077670	SOD	SOD	3.2	The toxicity of mutant SOD has been proposed to involve one or more of the
10077670	SOD	SOD	3.2	recently has been reported that the expression of FALS-associated mutant SOD in nerve growth factor (NGF)-differentiated NGF -differentiated PC12 cells primary
10077670	SOD	SOD-induced	2.4	The present study explores the relationship of mutant SOD-induced death to calcineurin a calcium/calmodulin-dependent calcium calmodulin-dependent phosphatase and characterizes
10077670	SOD	SOD	3.2	proline residues aids normal folding and assembly of proteins including SOD and has other cellular functions ( 15
10077670	SOD	SOD	3.2	A recent report demonstrated that SOD normally protects calcineurin from inactivation ( 16
10077670	SOD	SOD	3.2	The present investigation demonstrates that the proapoptotic activity of mutant SOD is not related to calcineurin inhibition
10077670	SOD	SOD	3.2	CsA CsG and FK506 enhance cell death induced by mutant SOD and that this enhancement depends on rotamase inhibition
10077670	SOD	SOD	3.2	These findings suggest that mutant SOD may lead to increased protein damage or turnover and a
10385054	SOD	SODs	2.7	Superoxide dismutases (SODs) SODs are enzymes that can influence free radical processes in irradiated
10385054	SOD	SODs	2.7	irradiated cells and there is some evidence that manipulation of SODs can affect survival of cells after radiation treatments
10385054	SOD1	SOD-1	10.2	SOD-1 associated FALS mutants may have an altered radiation response due
10385054	SOD1	SOD-1	10.2	ability of the lymphoblastoid cell lines from FALS patients with SOD-1 gene mutations patients with sporadic ALS and controls to handle
10385054	SOD1	SOD-1	10.2	radical-reactive fluorochrome in the cells from familial ALS patients with SOD-1 gene mutations (2.14_amp_#xb1;1.06 2.14_amp_#xb1 1.06 Gy _amp_#x2212 1 and patients
10385054	SOD1	SOD-1	10.2	The ability of lymphoblastoid cells from FALS patients with SOD-1 gene mutations to scavenge radiation-induced free radicals is not compromised
10385054	SOD1	SOD-1	10.2	and defects in the Cu/Zn Cu Zn superoxide dismutase (SOD-1) SOD-1 gene 2
10385054	SOD1	SOD-1	10.2	The SOD-1 gene encodes the cytosolic SOD-1 protein which catalyses the dismutation
10385054	SOD1	SOD-1	10.2	The SOD-1 gene encodes the cytosolic SOD-1 protein which catalyses the dismutation of superoxide anions (O O
10385054	SOD1	SOD-1	10.2	However SOD-1 can also generate free radicals 3 and SOD-1 associated FALS
10385054	SOD1	SOD-1	10.2	However SOD-1 can also generate free radicals 3 and SOD-1 associated FALS mutants have been shown to enhance the production
10385054	SOD	SOD	2.7	radicals 6 and it has been demonstrated that manipulation of SOD activity can influence the cellular radiation response 7
10385054	SOD1	SOD-1	10.2	Cells from FALS patients with mutations in the SOD-1 gene might therefore have a reduced tolerance of ROS and
10385054	SOD1	SOD-1	10.2	in lymphoblastoid cell-lines from FALS patients with mutations in the SOD-1 gene and to examine the ability of FALS cells to
10385054	SOD1	SOD-1	10.2	( n =2 and Gly 37 Arg ( n =1 SOD-1 gene mutations 8 and a known UK FALS patient with
10385054	SOD1	SOD-1	10.2	FALS patient with a Ile 149 Thr mutation in the SOD-1 gene 9 patients with sporadic ALS and matched spouse-controls were
10385054	SOD1	SOD-1	10.2	1 in the lymhpoblastoid cell lines from FALS patients with SOD-1 gene mutations were 1.50 and 1.26 ( Ala 4 Val
10385054	SOD1	SOD-1	10.2	DNA damage might be expected in lymphoblastoid cell lines with SOD-1 gene mutations
10385054	SOD1	SOD-1	10.2	reduced ability of lymphobiastoid cells from either FALS patients with SOD-1 gene mutations or from patients with sporadic ALS to cope
10385054	SOD1	SOD-1	10.2	production of hydroperoxides and double-strand DNA breaks is equivalent in SOD-1 associated FALS SALS and control lymphoblastoid cell lines
10385054	SOD	SOD	2.7	lines used in this study demonstrate a wide range of SOD activity regardless of the presence of the SOD-1 gene mutation
10385054	SOD1	SOD-1	10.2	range of SOD activity regardless of the presence of the SOD-1 gene mutation (data data not shown
10385054	SOD1	SOD-1	10.2	the hypothesis that a gain of an adverse function of SOD-1 rather than a loss of function may lead to motor
10385054	SOD1	SOD-1	10.2	An abnormal gain of function could enable SOD-1 to catalyse other reactions that are normally unfavorable e.g nitration
10385054	SOD1	SOD-1	10.2	1 in the lymphoblastoid cell lines of FALS patients with SOD-1 gene mutations (FALS), FALS patients with sporadic ALS (SALS) SALS
10385054	SOD1	SOD-1	10.2	1 in the lymphoblastoid cell lines of FALS patients with SOD-1 gene mutations (FALS), FALS patients with sporadic ALS (SALS) SALS
10593879	SOD1	SOD1	6.2	in mice transfected with a mutant Cu Zn-superoxide dismutase (SOD1) SOD1 gene from humans with familial ALS mice transfected with the
10593879	SOD1	SOD1	6.2	humans with familial ALS mice transfected with the normal human SOD1 gene and normal mice
10593879	SOD1	SOD1	6.2	impairment of its detoxification pathways perhaps by changed interactions between SOD1 and H 2 O 2 detoxification enzymes._amp_#151 Liu D. Wen
10593879	SOD1	SOD1	6.2	of a single-site mutation in the Cu Zn-superoxide dismutase (SOD1) SOD1 gene in familial ALS (FALS) FALS patients (2 2 3
10593879	SOD1	SOD1	6.2	To explore how mutant SOD1 (mSOD1) mSOD1 causes ALS Gurney and colleagues (5) 5 produced
10593879	SOD1	mSOD1	3.0	To explore how mutant SOD1 (mSOD1) mSOD1 causes ALS Gurney and colleagues (5) 5 produced a transgenic
10593879	SOD1	SOD1	6.2	model by introducing a human (with with ALS disease mutant SOD1 (mSOD1) mSOD1 gene (Gly Gly 93 Ala G93A into mice
10593879	SOD1	mSOD1	3.0	introducing a human (with with ALS disease mutant SOD1 (mSOD1) mSOD1 gene (Gly Gly 93 Ala G93A into mice these transfected
10593879	SOD1	SOD1	6.2	Since then over 50 different SOD1 mutants have been identified in FALS families (6) 6 and
10593879	SOD1	SOD1	6.2	Screening revealed SOD1 mutations with reduced SOD1 activity in 16 of 73 (22%)
10593879	SOD1	SOD1	6.2	Screening revealed SOD1 mutations with reduced SOD1 activity in 16 of 73 (22%) 22% ALS families (7)
10593879	SOD1	SOD1	6.2	22% ALS families (7) 7 suggesting that a loss of SOD1 function sometimes occurs in ALS
10593879	SOD1	SOD1	6.2	Mutations of the SOD1 gene reduce superoxide dismutase activity (2 2 3 8 9
10593879	SOD1	SOD1	6.2	found that transgenic mice expressing high levels of mutant human SOD1 protein became paralyzed even though the animal's own normal SOD1
10593879	SOD1	SOD1	6.2	SOD1 protein became paralyzed even though the animal's own normal SOD1 gene remained intact while similar overexpression of normal human SOD1
10593879	SOD1	SOD1	6.2	SOD1 gene remained intact while similar overexpression of normal human SOD1 did not produce ALS (5) 5
10593879	SOD1	SOD1	6.2	This result and the significantly increased expression of SOD1 mRNA in spinal cord motor neurons in sporadic ALS (13)
10593879	SOD1	mSOD1	3.0	motor neurons in sporadic ALS (13) 13 suggest that the mSOD1 protein gains a new function that damages motor neurons (5)
10593879	SOD1	SOD1	6.2	It has been demonstrated in vitro that SOD1 can catalyze dissociation of H 2 O 2 to OH
10593879	SOD1	mSOD1	3.0	OH (14 14 15 and that the OH-generating function of mSOD1 (G93A G93A and A4V is enhanced relative to that of
10593879	SOD1	SOD1	6.2	and A4V is enhanced relative to that of the normal SOD1 enzyme (16 16 17 18
10593879	SOD1	mSOD1	3.0	X-ray crystallographic studies show that the active channel of the mSOD1 containing copper and zinc is slightly larger than that of
10593879	SOD1	SOD1	6.2	and zinc is slightly larger than that of the normal SOD1 enzyme (3) 3 thus the metal atoms are more accessible
10593879	SOD1	SOD1	6.2	The mutant SOD1 might catalyze more OH formation because its Cu is more
10593879	SOD1	SOD1	6.2	there is strong disagreement regarding the possibility that the mutant SOD1 gains a new function to catalyze OH formation from H
10593879	SOD1	SOD1	6.2	OH levels are not significantly different between mutant (G37R) G37R SOD1 transgenic mice and controls (20) 20
10593879	SOD1	SOD1	6.2	(CSF) CSF in G93A transgenic mice than in normal and SOD1 transgenic mice (21) 21 and an elevated level of OH
10593879	SOD1	SOD1	6.2	is no difference in catalytic capability in vitro between mutant SOD1 and normal SOD1 in producing OH from H 2 O
10593879	SOD1	SOD1	6.2	in catalytic capability in vitro between mutant SOD1 and normal SOD1 in producing OH from H 2 O 2 questioning the
10593879	SOD1	SOD1	6.2	examined in vivo the in vitro finding that on mutation SOD1 gains a new function catalyzing OH formation from H 2
10593879	SOD1	mSOD1	3.0	the levels of ROS in the G93A transgenic mice (mSOD1 mSOD1 mice normal SOD1 transgenic mice (SOD1 SOD1 mice and normal
10593879	SOD1	SOD1	6.2	ROS in the G93A transgenic mice (mSOD1 mSOD1 mice normal SOD1 transgenic mice (SOD1 SOD1 mice and normal mice (or or
10593879	SOD1	SOD1	6.2	transgenic mice (mSOD1 mSOD1 mice normal SOD1 transgenic mice (SOD1 SOD1 mice and normal mice (or or the littermates of G93A
10593879	SOD1	mSOD1	3.0	indicate that the in vitro finding of OH formation by mSOD1 using H 2 O 2 as a substrate reported previously
10593879	SOD1	SOD1	6.2	in the spinal cord (32) 32 in mutant (G93A) G93A SOD1 transgenic mice
10593879	SOD1	SOD1	6.2	Our results support that the mutation of SOD1 indeed induces oxidative stress and correlate SOD1 mutation to elevated
10593879	SOD1	SOD1	6.2	the mutation of SOD1 indeed induces oxidative stress and correlate SOD1 mutation to elevated H 2 O 2 OH and oxidative
10593879	SOD1	SOD1	6.2	the Jackson laboratory were used mice transfected with the mutant SOD1 gene (G93A) G93A from humans with FALS-B6SJL-TgN(SOD1-G93A)1Gur,mice FALS-B6SJL-TgN SOD1-G93A 1Gur
10593879	SOD1	SOD1	6.2	with FALS-B6SJL-TgN(SOD1-G93A)1Gur,mice FALS-B6SJL-TgN SOD1-G93A 1Gur mice transfected with normal human SOD1 gene B6SJL-TgN(SOD1)2Gur, B6SJL-TgN SOD1 2Gur and normal control mice (B6SJLF1
10593879	SOD1	SOD1	6.2	1Gur mice transfected with normal human SOD1 gene B6SJL-TgN(SOD1)2Gur, B6SJL-TgN SOD1 2Gur and normal control mice (B6SJLF1 B6SJLF1 or littermates of
10593879	SOD1	mSOD1	3.0	2Gur and normal control mice (B6SJLF1 B6SJLF1 or littermates of mSOD1 and SOD1 mice without gene transfection
10593879	SOD1	SOD1	6.2	2Gur and normal control mice (B6SJLF1 B6SJLF1 or littermates of mSOD1 and SOD1 mice without gene transfection
10593879	SOD1	SOD1	6.2	normal control mice (B6SJLF1 B6SJLF1 or littermates of mSOD1 and SOD1 mice without gene transfection
10593879	SOD1	mSOD1	3.0	and MDA the onset of the ALS symptoms in the mSOD1 mice we used was delayed due to a small transgenic
10593879	SOD1	mSOD1	3.0	Therefore mSOD1 SOD1 and Nc mice were used at 6-6.5 months of
10593879	SOD1	SOD1	6.2	Therefore mSOD1 SOD1 and Nc mice were used at 6-6.5 months of age
10593879	SOD1	mSOD1	3.0	The mSOD1 mice used for the measurement of O 2 and H
10593879	SOD1	mSOD1	3.0	by 4-5 months for those mutants therefore 2.5- to 3-month-old mSOD1 mice and matching age SOD1 and Nc mice were used
10593879	SOD1	SOD1	6.2	mutants therefore 2.5- to 3-month-old mSOD1 mice and matching age SOD1 and Nc mice were used while paralysis was developing in
10593879	SOD1	mSOD1	3.0	levels of O 2 were different among the littermates of mSOD1 mice littermates of SOD1 mice and the normal control mice
10593879	SOD1	SOD1	6.2	were different among the littermates of mSOD1 mice littermates of SOD1 mice and the normal control mice (B6SJLF1); B6SJLF1 no difference
10593879	SOD1	mSOD1	3.0	the B6SJLF1 normal control mice are a valid control for mSOD1 mice our definition of normal control (Nc) Nc mice includes
10593879	SOD1	mSOD1	3.0	control (Nc) Nc mice includes B6SJLF1 mice and littermates of mSOD1 and SOD mice
10593879	SOD	SOD	1.9	Nc mice includes B6SJLF1 mice and littermates of mSOD1 and SOD mice
10593879	SOD1	SOD1	6.2	The mutation of SOD1 significantly increases the levels of OH
10593879	SOD1	mSOD1	3.0	5-DHBA (mean_amp_#177; mean_amp_#177 SD is 980 _amp_#177 240 nM in mSOD1 mice ( n =8 300 _amp_#177 120 nM in SOD1
10593879	SOD1	SOD1	6.2	mSOD1 mice ( n =8 300 _amp_#177 120 nM in SOD1 mice ( n =5 and 400 _amp_#177 190 nM in
10593879	SOD1	mSOD1	3.0	nM in Nc mice ( n =6 ~3.3-fold higher in mSOD1 mice than in SOD1 mice ( P =0.0001 and 2.5-fold
10593879	SOD1	SOD1	6.2	( n =6 ~3.3-fold higher in mSOD1 mice than in SOD1 mice ( P =0.0001 and 2.5-fold higher than in Nc
10593879	SOD1	mSOD1	3.0	3-DHBA (mean_amp_#177; mean_amp_#177 SD is 650 _amp_#177 130 nM in mSOD1 mice 330 _amp_#177 90 nM in SOD1 mice and 350
10593879	SOD1	SOD1	6.2	130 nM in mSOD1 mice 330 _amp_#177 90 nM in SOD1 mice and 350 _amp_#177 190 nM in Nc mice ~2.0-fold
10593879	SOD1	mSOD1	3.0	350 _amp_#177 190 nM in Nc mice ~2.0-fold higher in mSOD1 mice than in SOD1 mice ( P =0.0006 and 1.9-fold
10593879	SOD1	SOD1	6.2	in Nc mice ~2.0-fold higher in mSOD1 mice than in SOD1 mice ( P =0.0006 and 1.9-fold higher than in Nc
10593879	SOD1	mSOD1	3.0	Both 2,5- and 2 3-DHBA levels are significantly higher in mSOD1 mice than in SOD1 and Nc mice but there is
10593879	SOD1	SOD1	6.2	3-DHBA levels are significantly higher in mSOD1 mice than in SOD1 and Nc mice but there is no significant difference between
10593879	SOD1	SOD1	6.2	Nc mice but there is no significant difference between the SOD1 and Nc mice ( P =0.3 for 2 5-DHBA and
10593879	SOD1	SOD1	6.2	and 0.8 for 2 3-DHBA direct in vivo evidence that SOD1 mutation elevates the levels of OH
10593879	SOD1	SOD1	6.2	the first time using G93A transgenic mice that mutation of SOD1 elevates levels of both H 2 O 2 and OH
10593879	SOD1	SOD1	6.2	H 2 O 2 level is increased in the mutant SOD1 transgenic mice but not in the mice overexpressing normal human
10593879	SOD1	SOD1	6.2	transgenic mice but not in the mice overexpressing normal human SOD1 is particularly important with significant implications about the pathogenesis of
10593879	SOD1	mSOD1	3.0	hypothesis and indicate that the new function gained by the mSOD1 includes both catalyzing H 2 O 2 conversion to OH
10593879	SOD1	mSOD1	3.0	20 appeared to rule out elevation of OH production in mSOD1 transgenic mice and reports (18 18 23 as to whether
10593879	SOD1	SOD1	6.2	mice and reports (18 18 23 as to whether mutant SOD1 catalyzes increased production of OH from H 2 O 2
10593879	SOD1	SOD1	6.2	However in our in vivo results mutation of SOD1 clearly raised H 2 O 2 levels and induced more
10593879	SOD1	mSOD1	3.0	greater ratio of OH]/[H OH H 2 O 2 in mSOD1 mice (0.23) 0.23 than in SOD1 and Nc mice (0.17
10593879	SOD1	SOD1	6.2	2 O 2 in mSOD1 mice (0.23) 0.23 than in SOD1 and Nc mice (0.17 0.17 and 0.16 respectively supports the
10593879	SOD1	mSOD1	3.0	mice (0.17 0.17 and 0.16 respectively supports the notion that mSOD1 mice have a higher capability of converting H 2 O
10593879	SOD1	SOD1	6.2	capability of converting H 2 O 2 to OH than SOD1 and Nc mice do
10593879	SOD1	SOD1	6.2	SOD1 mice contain both the SOD1 enzyme from the transfected normal
10593879	SOD1	SOD1	6.2	SOD1 mice contain both the SOD1 enzyme from the transfected normal human SOD1 (hSOD1) hSOD1 gene
10593879	SOD1	SOD1	6.2	contain both the SOD1 enzyme from the transfected normal human SOD1 (hSOD1) hSOD1 gene and the mouse's own SOD1 (endogenous endogenous
10593879	SOD1	hSOD1	1.9	the SOD1 enzyme from the transfected normal human SOD1 (hSOD1) hSOD1 gene and the mouse's own SOD1 (endogenous endogenous SOD1 eSOD1
10593879	SOD1	SOD1	6.2	normal human SOD1 (hSOD1) hSOD1 gene and the mouse's own SOD1 (endogenous endogenous SOD1 eSOD1 mSOD1 mice contain the G93A mutant
10593879	SOD1	SOD1	6.2	(hSOD1) hSOD1 gene and the mouse's own SOD1 (endogenous endogenous SOD1 eSOD1 mSOD1 mice contain the G93A mutant SOD1 and eSOD1
10593879	SOD1	mSOD1	3.0	gene and the mouse's own SOD1 (endogenous endogenous SOD1 eSOD1 mSOD1 mice contain the G93A mutant SOD1 and eSOD1 whereas Nc
10593879	SOD1	SOD1	6.2	(endogenous endogenous SOD1 eSOD1 mSOD1 mice contain the G93A mutant SOD1 and eSOD1 whereas Nc mice contain only eSOD1
10593879	SOD1	SOD1	6.2	thereby reduce the level of O 2 has the order SOD1 mice > mSOD1 mice > Nc mice and the opposite
10593879	SOD1	mSOD1	3.0	level of O 2 has the order SOD1 mice > mSOD1 mice > Nc mice and the opposite order for the
10593879	SOD1	mSOD1	3.0	order for the level of O 2 Nc mice > mSOD1 mice > SOD1 mice
10593879	SOD1	SOD1	6.2	level of O 2 Nc mice > mSOD1 mice > SOD1 mice
10593879	SOD1	SOD1	6.2	All together our results demonstrate that the mutation of SOD1 induced more OH formation from elevated H 2 O 2
10593879	SOD1	SOD1	6.2	H 2 O 2 may be converted to OH by SOD1
10593879	SOD1	SOD1	6.2	ability more H 2 O 2 should be produced in SOD1 mice however no accumulation of H 2 O 2 was
10593879	SOD1	SOD1	6.2	no accumulation of H 2 O 2 was observed in SOD1 mice compared to Nc mice
10593879	SOD1	mSOD1	3.0	which is the normal catalytic function of GSH-Px and catalase mSOD1 mice had significantly higher levels of H 2 O 2
10593879	SOD1	SOD1	6.2	of H 2 O 2 and OH than did the SOD1 and Nc mice and significantly lower levels of O 2
10593879	SOD1	mSOD1	3.0	This suggests that mSOD1 gains a new function blocking H 2 O 2 conversion
10593879	SOD1	SOD1	6.2	O 2 caused by increasing or decreasing levels of wild-type SOD1
10593879	SOD1	hSOD1	1.9	Because overexpression of hSOD1 or knocking out eSOD1 did not change the onset and
10593879	SOD1	SOD1	6.2	of mice show that although addition of mutant and normal SOD1 both decrease O 2 concentrations concentrations of H 2 O
10593879	SOD1	SOD1	6.2	2 increase with the presence of mutated but not normal SOD1 contrary to their assumption
10593879	SOD1	hSOD1	1.9	results that H 2 O 2 formed by overexpression of hSOD1 is efficiently destroyed whereas more of that produced by the
10593879	SOD1	SOD1	6.2	efficiently destroyed whereas more of that produced by the mutant SOD1 escapes into the tissue where it may produce damaging OH
10593879	SOD1	SOD1	6.2	O 2 detoxification pathway a crucial change whereby mutation of SOD1 leads to ALS
10593879	SOD1	mSOD1	3.0	possible to discover this problem in vitro by using purified mSOD1
10593879	SOD1	SOD1	6.2	The deleterious SOD1 mutations typically are in the interaction regions crucial to subunit
10593879	SOD1	SOD1	6.2	folding and dimer contact (3) 3 explaining why there is SOD1 aggregation only in the G93A and G85R transgenic mice but
10593879	SOD1	SOD1	6.2	and G85R transgenic mice but not in the mice overexpressing SOD1 (19) 19
10593879	SOD1	SOD1	6.2	The SOD1 dimer may act in tandem as a superoxide dismutase and
10593879	SOD1	mSOD1	3.0	evidenced by the accumulation of H 2 O 2 in mSOD1 mice
10593879	SOD1	SOD1	6.2	radicals their work supports a relationship between free radicals and SOD1 mutation in FALS
10593879	SOD1	SOD1	6.2	2 O 2 of fibroblasts from FALS patients with an SOD1 mutation is higher than for controls suggests that the mechanism
10593879	SOD1	mSOD1	3.0	O 2 levels in the dialysates are also elevated in mSOD1 mice is consistent with this explanation since H 2 O
10593879	SOD1	mSOD1	3.0	level of H 2 O 2 in the cells in mSOD1 mice
10593879	SOD1	mSOD1	3.0	The elevated level of H 2 O 2 in mSOD1 mice supports the notion that the increased levels of OH
10593879	SOD1	SOD1	6.2	partly formed from H 2 O 2 by the mutant SOD1 however a contribution of peroxynitrate cannot be ruled out since
10593879	SOD1	mSOD1	3.0	we have found that the level of nitric oxide in mSOD1 mice is also significantly higher than in SOD1 and Nc
10593879	SOD1	SOD1	6.2	oxide in mSOD1 mice is also significantly higher than in SOD1 and Nc mice (65) 65
10593879	SOD1	hSOD1	1.9	Based on the observations that overexpression of hSOD1 did not change the onset and progress of the disease
10593879	SOD1	SOD1	6.2	It has been suggested that the deleterious effect of mutant SOD1 on motor neurons in ALS is not related to increased
10593879	SOD1	mSOD1	3.0	of protein DNA and membrane lipids are significantly higher in mSOD1 mice than in SOD1 and Nc mice but not between
10593879	SOD1	SOD1	6.2	membrane lipids are significantly higher in mSOD1 mice than in SOD1 and Nc mice but not between SOD1 and Nc mice
10593879	SOD1	SOD1	6.2	mice than in SOD1 and Nc mice but not between SOD1 and Nc mice is consistent with some other reports (8
10593879	SOD1	mSOD1	3.0	membrane lipid oxidation together with elevated level of OH in mSOD1 mice support the hypothesis that OH-triggered oxidation of major cell
10593879	SOD1	SOD1	6.2	been revealed the finding that there are higher levels of SOD1 in motoneurons relative to other neurons (66) 66 implicates a
10593879	SOD1	mSOD1	3.0	selective degeneration of motoneurons in ALS because higher levels of mSOD1 are probably present in those neurons relative to others when
10593879	SOD1	mSOD1	3.0	EC detection in the three groups of mice (8 8 mSOD1 5 SOD1 and 6 Nc mice
10593879	SOD1	SOD1	6.2	in the three groups of mice (8 8 mSOD1 5 SOD1 and 6 Nc mice
10593879	SOD1	mSOD1	3.0	b Chromatogram of 10 microl dialysate obtained from a mSOD1 mouse
10593879	SOD1	SOD1	6.2	c Chromatogram of 10 microl dialysate obtained from a SOD1 mouse
10593879	SOD1	mSOD1	3.0	of reduced cytochrome c measured in the perfusates collected from mSOD1 ( n =6 SOD1 ( n =3 and Nc mice
10593879	SOD1	SOD1	6.2	measured in the perfusates collected from mSOD1 ( n =6 SOD1 ( n =3 and Nc mice ( n =6
10593879	SOD1	mSOD1	3.0	of reduced cytochrome c measured in spinal cord tissue in mSOD1 ( n =3 SOD1 ( n =3 and Nc mice
10593879	SOD1	SOD1	6.2	measured in spinal cord tissue in mSOD1 ( n =3 SOD1 ( n =3 and Nc mice ( n =4
10593879	SOD1	mSOD1	3.0	in microdialysates was measured by HPLC and fluorescence detection in mSOD1 ( n =8 SOD1 ( n =7 and Nc (
10593879	SOD1	SOD1	6.2	by HPLC and fluorescence detection in mSOD1 ( n =8 SOD1 ( n =7 and Nc ( n =9 mice
10593879	SOD1	mSOD1	3.0	Protein carbonyl content in the mouse spinal cord tissue of mSOD1 SOD1 and Nc mice was measured spectrophotometrically after labeling with
10593879	SOD1	SOD1	6.2	carbonyl content in the mouse spinal cord tissue of mSOD1 SOD1 and Nc mice was measured spectrophotometrically after labeling with DNPH
10593879	SOD1	mSOD1	3.0	all measurements to determine whether the mean results obtained from mSOD1 SOD1 and Nc mice were significantly different
10593879	SOD1	SOD1	6.2	measurements to determine whether the mean results obtained from mSOD1 SOD1 and Nc mice were significantly different
10593879	SOD1	SOD1	6.2	The mutation of SOD1 significantly increases the levels of H 2 O 2
10593879	SOD1	mSOD1	3.0	2 (mean_amp_#177; mean_amp_#177 SD is 2.8 _amp_#177 0.3 microM in mSOD1 mice ( n =4 1.9 _amp_#177 0.2 microM in SOD1
10593879	SOD1	SOD1	6.2	mSOD1 mice ( n =4 1.9 _amp_#177 0.2 microM in SOD1 mice ( n =3 and 2.1 _amp_#177 0.4 microM in
10593879	SOD1	mSOD1	3.0	levels of H 2 O 2 are significantly higher in mSOD1 mice than in SOD1 ( P =0.005 and Nc mice
10593879	SOD1	SOD1	6.2	O 2 are significantly higher in mSOD1 mice than in SOD1 ( P =0.005 and Nc mice ( P =0.007 but
10593879	SOD1	SOD1	6.2	P =0.007 but there is no significant difference between the SOD1 and Nc mice ( P =0.6 indicating that mutant SOD1in
10593879	SOD1	mSOD1	3.0	Nc mice ( P =0.6 indicating that mutant SOD1in the mSOD1 mice also elevates H 2 O 2 levels
10593879	SOD1	mSOD1	3.0	levels of O 2 in the perfusates collected from the mSOD1 SOD1 and Nc mice
10593879	SOD1	SOD1	6.2	of O 2 in the perfusates collected from the mSOD1 SOD1 and Nc mice
10593879	SOD1	mSOD1	3.0	cytochrome c (mean_amp_#177; mean_amp_#177 SD is 0.060 _amp_#177 0.011 in mSOD1 mice ( n =6 0.037 _amp_#177 0.004 in SOD1 mice
10593879	SOD1	SOD1	6.2	in mSOD1 mice ( n =6 0.037 _amp_#177 0.004 in SOD1 mice ( n =3 and 0.130 _amp_#177 0.030 in Nc
10593879	SOD1	mSOD1	3.0	2 are significantly higher in normal control mice than in mSOD1 ( P =0.0007 and SOD1 mice ( P =0.002
10593879	SOD1	SOD1	6.2	normal control mice than in mSOD1 ( P =0.0007 and SOD1 mice ( P =0.002
10593879	SOD1	mSOD1	3.0	The level of O 2 is also significantly higher in mSOD1 than in SOD1 mice ( P =0.01
10593879	SOD1	SOD1	6.2	O 2 is also significantly higher in mSOD1 than in SOD1 mice ( P =0.01
10593879	SOD1	mSOD1	3.0	of O 2 in the spinal cord tissue of the mSOD1 SOD1 and Nc mice
10593879	SOD1	SOD1	6.2	O 2 in the spinal cord tissue of the mSOD1 SOD1 and Nc mice
10593879	SOD1	mSOD1	3.0	absorbance g wet weight tissue is 158 _amp_#177 10 in mSOD1 mice ( n =3 138 _amp_#177 10 in SOD1 mice
10593879	SOD1	SOD1	6.2	in mSOD1 mice ( n =3 138 _amp_#177 10 in SOD1 mice ( n =3 and 186 _amp_#177 12 in Nc
10593879	SOD1	mSOD1	3.0	tissue of normal control mice is significantly higher than in mSOD1 ( P =0.02 and SOD1 mice ( P =0.003 and
10593879	SOD1	SOD1	6.2	is significantly higher than in mSOD1 ( P =0.02 and SOD1 mice ( P =0.003 and is also higher in mSOD1
10593879	SOD1	mSOD1	3.0	SOD1 mice ( P =0.003 and is also higher in mSOD1 than in SOD1 mice
10593879	SOD1	SOD1	6.2	P =0.003 and is also higher in mSOD1 than in SOD1 mice
10593879	SOD1	SOD1	6.2	Mutation of SOD1 significantly increases membrane peroxidation
10593879	SOD1	mSOD1	3.0	of MDA in the dialysates collected from the CSF in mSOD1 SOD1 and Nc mice
10593879	SOD1	SOD1	6.2	MDA in the dialysates collected from the CSF in mSOD1 SOD1 and Nc mice
10593879	SOD1	mSOD1	3.0	MDA (mean_amp_#177; mean_amp_#177 SD is 70 _amp_#177 15 nM in mSOD1 mice ( n =8 40 _amp_#177 5 nM in SOD1
10593879	SOD1	SOD1	6.2	mSOD1 mice ( n =8 40 _amp_#177 5 nM in SOD1 mice ( n =7 and 30 _amp_#177 10 nM in
10593879	SOD1	mSOD1	3.0	The MDA level in dialysates in mSOD1 mice is 1.8-fold that in SOD1 mice ( P =0.0005
10593879	SOD1	SOD1	6.2	level in dialysates in mSOD1 mice is 1.8-fold that in SOD1 mice ( P =0.0005 and 2.3-fold higher than in Nc
10593879	SOD1	SOD1	6.2	There was no significant difference between SOD1 and Nc mice ( P =0.1 suggesting that overexpression of
10593879	SOD1	SOD1	6.2	Nc mice ( P =0.1 suggesting that overexpression of normal SOD1 does not increase peroxidation of membrane lipids
10593879	SOD1	mSOD1	3.0	The significantly higher levels of MDA in mSOD1 mice than in SOD1 and Nc mice demonstrate that oxidative
10593879	SOD1	SOD1	6.2	significantly higher levels of MDA in mSOD1 mice than in SOD1 and Nc mice demonstrate that oxidative damage to membrane phospholipids
10593879	SOD1	SOD1	6.2	membrane phospholipids indeed occurs after the induction of the mutant SOD1 gene
10593879	SOD1	SOD1	6.2	The mutation of SOD1 significantly increases protein oxidation
10593879	SOD1	mSOD1	3.0	SD is 2.31 _amp_#177 0.16 nmol/mg nmol mg protein in mSOD1 mice 1.95 _amp_#177 0.09 nmol/mg nmol mg protein in SOD1
10593879	SOD1	SOD1	6.2	mSOD1 mice 1.95 _amp_#177 0.09 nmol/mg nmol mg protein in SOD1 mice and 1.94 _amp_#177 0.13 nmol/mg nmol mg in Nc
10593879	SOD1	mSOD1	3.0	carbonyl content in spinal cord tissue is 1.2-fold higher in mSOD1 mice than in SOD1 ( P =0.0002 and Nc (
10593879	SOD1	SOD1	6.2	cord tissue is 1.2-fold higher in mSOD1 mice than in SOD1 ( P =0.0002 and Nc ( P =0.0004 mice_amp_#151 a
10593879	SOD1	SOD1	6.2	two controls ( P =0.9 indicating that overexpression of normal SOD1 does not induce protein oxidation and only mutant SOD1 in
10593879	SOD1	SOD1	6.2	normal SOD1 does not induce protein oxidation and only mutant SOD1 in mSOD1 mice causes significantly more protein oxidation
10593879	SOD1	mSOD1	3.0	does not induce protein oxidation and only mutant SOD1 in mSOD1 mice causes significantly more protein oxidation
10593879	SOD1	SOD1	6.2	The mutation of SOD1 significantly increases DNA oxidation
10593879	SOD1	mSOD1	3.0	The average concentration (from from three samples of 8-OHdG in mSOD1 mice is 0.27 _amp_#177 0.06 fmol/mg fmol mg wet tissue
10593879	SOD1	mSOD1	3.0	_amp_#177 0.12 fmol/microg fmol microg DNA (mean_amp_#177; mean_amp_#177 SD 10 mSOD1 mouse spinal cords were measured as three samples 8-OHdG was
10593879	SOD1	SOD1	6.2	8-OHdG was undetectable in the same amount of tissue from SOD1 or Nc mice
10593879	SOD1	mSOD1	3.0	Thus DNA oxidation occurs in mSOD1 mice
10593879	SOD1	SOD1	6.2	and reduction of O 2 in the presence of mutant SOD1
10593879	SOD1	SOD1	6.2	by in vivo experiments the in vitro discovery that mutant SOD1 gains a new function catalyzing more OH production from H
10593879	SOD1	SOD1	6.2	also indicate that the new function gained by the mutant SOD1 enzyme is not only catalyzing more OH formation but also
10671549	SOD	SOD	2.4	The enzyme superoxide dismutase (SOD) SOD may play a fundamental role in modulating NO toxicity since
10671549	SOD	SOD	2.4	As matter of fact cells producing an increased amount of SOD were resistant to NO-mediated toxicity ( 24
10671549	SOD	SOD	2.4	sclerosis (FALS FALS are pro-apoptotic agents although they retain enzymatic SOD activity ( 26
10671549	SOD	SOD	2.4	Cells carrying wild type SOD are protected from NO-mediated apoptosis whereas cells transfected with the
10671549	SOD	SOD	2.4	protected from NO-mediated apoptosis whereas cells transfected with the mutant SOD are more susceptible
10671549	SOD	SOD	2.4	type Cu Zn-SOD (named named WT or with a mutated SOD G93A (named named G93A were obtained as described previously (
10671549	SOD	SOD	2.4	Supernatants were used for SOD activity and protein content assay
10671549	SOD	SOD	2.4	However cells transfected with normal SOD were much less protected than against NO-mediated apoptosis
10671549	SOD	SOD	2.4	be strengthened by O 2 via formation of peroxynitrite and SOD that catalytically removes O 2 is therefore indicated as a
10671549	SOD	SOD	2.4	However cells transfected with a SOD mutant (G93A G93A as active as the wild type were
10671549	SOD	SOD	2.4	NO-mediated apoptosis and that additional properties of the G93A mutant SOD potentiate apoptogenic stimuli of NO
10671549	SOD	SOD	2.4	a factor protecting neurons from NO-induced apoptosis whereas the G93A SOD mutant despite high dismutating activity increased intracellular flux of ROS
10671549	SOD	SOD	2.4	SOD activity (not not shown and protein levels of WT and
10671549	SOD	SOD	2.4	Furthermore SOD activity of the three cell lines was unaffected by GSNO
10671549	SOD	SOD	2.4	by GSNO treatment (not not shown as well as the SOD protein content as assessed by Western blot analysis (Fig Fig
10671549	SOD	SOD	2.4	apoptosis of G93A cells cannot be explained in terms of SOD level
10671549	SOD	SOD	2.4	or hydroxyl radical formation has been demonstrated for fully active SOD mutants associated with FALS ( 47
10671549	SOD	SOD	2.4	not significantly affected either by the transfection with the mutant SOD or by the GSNO treatment
10742195	SOD	SOD	1.4	essential role in loading Cu 2 onto superoxide dismutase (SOD)1 SOD 1 under conditions of low cytosolic Cu 2 8
10742195	SOD1	SOD1	1.9	it shows that the cell possesses machinery to ensure that SOD1 antioxidant activity (which which depends upon a Cu 2 catalytic
10742195	SOD1	SOD1	1.9	It is proposed that although SOD1 has a very high affinity (femtomolar) femtomolar Cu 2 -binding
10742195	SOD1	SOD1	1.9	atom per cell that CCS facilitates Cu 2 loading onto SOD1 by competing against the pool of cytosolic Cu 2 scavengers
10742195	SOD1	SOD1	1.9	resembling the metallochaperone protein Atx1 and a second domain resembling SOD1 itself but lacking its metal-binding sites and catalytic-site residues 9
10742195	SOD1	SOD1	1.9	unlikely to play any role in disease biochemistry outside of SOD1
10742195	SOD1	SOD1	1.9	Familial amyotrophic lateral sclerosis SOD1 and copper
10742195	SOD	SOD	1.4	the elucidation of how a mutation of Cu/Zn Cu Zn SOD (SOD1) SOD1 engenders a gain of function that changes this
10742195	SOD1	SOD1	1.9	of how a mutation of Cu/Zn Cu Zn SOD (SOD1) SOD1 engenders a gain of function that changes this ubiquitous antioxidant
10742195	SOD1	SOD1	1.9	abundant literature on the oxidative insult caused by the FALS-linked SOD1 mutation 15 and 16 as well as the formation of
10742195	SOD1	SOD1	1.9	mutation 15 and 16 as well as the formation of SOD1 aggregates in affected motor neurons and glia 17
10742195	SOD1	SOD1	1.9	I believe will become fundamental not only to understanding how SOD1 mutations cause FALS but also how well known toxic proteins
10742195	SOD	SOD	1.4	Alone it has a SOD activity with a rate constant the same as SOD1 itself
10742195	SOD1	SOD1	1.9	a SOD activity with a rate constant the same as SOD1 itself 18
10742195	SOD1	SOD1	1.9	The purpose of the SOD1 protein is to harness this activity of Cu 2 without
10742195	SOD1	SOD1	1.9	Hence the Cu 2 at the active site of SOD1 has the potential to be abnormally redox reactive generating unwanted
10742195	SOD1	SOD1	1.9	19 describing a likely mechanism for the pathogenicity of mutant SOD1
10742195	SOD1	SOD1	1.9	The pathogenic SOD1 mutations do not cause a loss of function when the
10742195	SOD	SOD	1.4	al 19 observed that altered Cu 2 coordination made Zn-deficient SOD (wild wild type or mutant a more efficient oxidant able
10742195	SOD	SOD	1.4	The altered reactivity of Zn-deficient SOD enables it to be reduced by cellular reductants (such such
10742195	SOD	SOD	1.4	SOD then donates an electron to O 2 to generate O
10742195	SOD1	SOD1	1.9	Thus if SOD1 loses Zn 2 its catalytic activity is diminished while it
10742195	SOD1	SOD1	1.9	The O 2 _amp_#x2212 formed by Zn-deficient SOD1 might not be released as a free intermediate which would
10742195	SOD1	SOD1	1.9	released as a free intermediate which would explain why excess SOD1 fails to slow disease progression in FALS/SOD1 FALS SOD1 transgenic
10742195	SOD1	SOD1	1.9	excess SOD1 fails to slow disease progression in FALS/SOD1 FALS SOD1 transgenic mice 17
10742195	SOD1	SOD1	1.9	Intriguingly Estevez et al 19 found that apo SOD1 was not neurotoxic in cell culture whereas Zn-deficient Cu-loaded SOD1
10742195	SOD1	SOD1	1.9	SOD1 was not neurotoxic in cell culture whereas Zn-deficient Cu-loaded SOD1 was neurotoxic an effect that could be rescued by treatment
10742195	SOD1	SOD1	1.9	the treatment efficacy of Cu 2 chelators upon FALS/SOD1 FALS SOD1 transgenic mice 22
10742195	SOD	SOD-like	1.4	cell-culture data indicate that Cu/Zn-loaded Cu Zn-loaded A_amp_#x3b2 possesses catalytic SOD-like activity and that A_amp_#x3b2 1-42 has greater activity than A_amp_#x3b2
10742195	SOD1	SOD1	1.9	be mechanistically related to the oxidative stress induced by mutant SOD1
10742195	SOD	SOD	1.4	by David Brown et al 35 that PrP c possesses SOD activity
10742195	SOD	SOD	1.4	The SOD activity of PrP c is also intriguing because of the
10742195	SOD1	SOD1	1.9	Like mutant SOD1 PrP sc might be a modification of PrP that induces
10742195	SOD1	SOD1	1.9	In normal SOD1 Cu A_amp_#x3b2 or PrP c the Cu 2 active site
10742195	SOD	SOD	1.4	A manganese SOD SOD2 is the mitochondrial equivalent of SOD1 preventing O 2
10742195	SOD1	SOD1	1.9	A manganese SOD SOD2 is the mitochondrial equivalent of SOD1 preventing O 2 _amp_#x2212 from reacting with sensitive substrates such
10795881	SOD1	SOD1	1.4	In one or two percentage of patients mutations in the SOD1 gene are known to underly the disease
10795881	SOD1	SOD1-related	0.9	evidence for oxidative stress is not only found in mutant SOD1-related familial amyotrophic lateral sclerosis but also in sporadic amyotrophic lateral
10826922	SOD	SODs	1.4	Eight mutant Cu Zn-superoxide dismutases (SODs) SODs related to familial amyotrophic lateral sclerosis (FALS) FALS were produced
10826922	SOD	SOD	1.4	with Chelex 100 resin decreased Cu contents as well as SOD activities in all mutant Cu Zn-SODs indicating that the affinities
10826922	SOD	SOD	1.4	Both SOD activities and their reactive oxidant forming correlated well with the
10826922	SOD1	SOD1	1.4	Since hyaline inclusions found in FALS patients with SOD1 mutations contained components which were reactive to anti-Cu Zn-SOD antibody
10826922	SOD1	SOD1	1.4	to anti-Cu Zn-SOD antibody a primary reaction caused by mutant SOD1 may be attributed to their propensity to form aggregates
10826922	SOD1	SOD1	1.4	Aggregated but still active mutant SOD1 would be expected to mediate the formation of reactive oxygen
10899935	SOD1	SOD1	0.9	by overexpression of wild-type antioxidant Cu Zn superoxide dismutase (SOD1) SOD1 that promotes CN activity and protects it from oxidative inactivation
10899935	SOD1	SOD1s	0.9	On the contrary overexpression of mutant SOD1s associated with familial amyotrophic lateral sclerosis (FALS) FALS impairs CN
10899935	SOD1	SOD1-linked	0.9	that CN might be a target in the pathogenesis of SOD1-linked FALS
10930589	SOD1	SOD1	5.1	is associated with more than 70 different mutations in the SOD1 gene
10930589	SOD1	SOD1	5.1	lines derived from FALS patients with 16 different mutations in SOD1 gene exhibit significant increase of intracellular reactive oxygen species (ROS)
10930589	SOD1	SOD1	5.1	The ROS generation did not correlate with SOD1 activity
10930589	SOD1	SOD1	5.1	increased H 2 O 2 could be generated by mutant SOD1
10930589	SOD1	SOD1	5.1	in the gene for cytosolic Cu Zn superoxide dismutase ( SOD1 CuZnSOD 1 and 2
10930589	SOD1	SOD1	5.1	SOD1 functions as a homodimeric enzyme that is widely expressed and
10930589	SOD1	SOD1	5.1	The mechanisms by which SOD1 mutations cause selective motor neuron degeneration is not clearly understood
10930589	SOD1	SOD1	5.1	However SOD1 activity in red blood cells of most SOD1 mutant heterozygotes
10930589	SOD1	SOD1	5.1	However SOD1 activity in red blood cells of most SOD1 mutant heterozygotes is reduced
10930589	SOD1	SOD1	5.1	be less than 50% in some cases suggesting that mutant SOD1 may affect the activity of the wildtype enzyme 2 3
10930589	SOD1	SOD1	5.1	Evidence from SOD1 transgenic mice and SOD1 knockout mice suggests that reduced dismutase
10930589	SOD1	SOD1	5.1	Evidence from SOD1 transgenic mice and SOD1 knockout mice suggests that reduced dismutase activity is not the
10930589	SOD1	SOD1	5.1	Decreased SOD1 activity in ALS patients would be expected to lead to
10930589	SOD1	SOD1	5.1	Mutant SOD1 was shown to have increased peroxidase activity over wildtype SOD1
10930589	SOD1	SOD1	5.1	SOD1 was shown to have increased peroxidase activity over wildtype SOD1 in vitro
10930589	SOD1	SOD1	5.1	Thus mutant SOD1 may produce more free radicals than wild SOD1 7
10930589	SOD1	SOD1	5.1	Thus mutant SOD1 may produce more free radicals than wild SOD1 7
10930589	SOD1	SOD1	5.1	show any difference in peroxidase activity of mutant and wildtype SOD1 8 and 9
10930589	SOD1	SOD1	5.1	was shown this discrepancy was due to different preparations of SOD1 proteins and experimental conditions 8 and 9
10930589	SOD1	SOD1	5.1	(ROS) ROS in lymphoblast cell lines derived from patients with SOD1 linked FALS sporadic ALS and normal controls (spouses spouses of
10930589	SOD1	SOD1	5.1	were similar in all groups despite a 45% decrease in SOD1 activity in FALS mutants
10930589	SOD	SOD	2.2	SOD assay
10930589	SOD	SOD	2.2	Total SOD activity was determined by its ability to catalyze the disproportionation
10930589	SOD1	SOD1	5.1	No significant correlation was observed between relative C-DCF fluorescence and SOD1 activity in all groups at resting levels
10930589	SOD1	SOD1	5.1	with menadione showed an inverse correlation of C-DCF fluorescence with SOD1 activity ( r =0.6 P _amp_#x3c 0.001 ( Table 1
10930589	SOD1	SOD1	5.1	is unlikely to be increased in FALS cells despite reduced SOD1 activity
10930589	SOD1	SOD1	5.1	Previous studies have shown that SOD1 is inhibited by a number of metal chelating agents e.g
10930589	SOD1	SOD1	5.1	Reaction of SOD1 with DDC requires two molecule of DDC (i) i one
10930589	SOD1	SOD1	5.1	(i) i one molecule interacts with the copper center of SOD1 with retention of activity (ii) ii while a second molecule
10930589	SOD1	SOD1	5.1	This suggests the interaction of DDC with mutant SOD1 may be altered and that wildtype SOD1 contributes approximately 30_amp_#x2013
10930589	SOD1	SOD1	5.1	DDC with mutant SOD1 may be altered and that wildtype SOD1 contributes approximately 30_amp_#x2013 50% of C-DCF fluorescence in resting cells
10930589	SOD1	SOD1	5.1	SOD1 is a major source of H 2 O 2 in
10930589	SOD1	SOD1	5.1	Since mutations in SOD1 are associated with FALS and activity of SOD1 is decreased
10930589	SOD1	SOD1	5.1	mutations in SOD1 are associated with FALS and activity of SOD1 is decreased (primarily primarily due to decreased half life of
10930589	SOD1	SOD1	5.1	decreased (primarily primarily due to decreased half life of mutant SOD1 we investigated whether this would lead to increased free radical
10930589	SOD1	SOD1	5.1	O 2 ._amp_#x2212 is cleared very quickly from cells by SOD1 28 even when SOD1 is reduced by 50%
10930589	SOD1	SOD1	5.1	cleared very quickly from cells by SOD1 28 even when SOD1 is reduced by 50%
10930589	SOD1	SOD1	5.1	Our hypothesis is that copper in mutant SOD1 is available to O 2 ._amp_#x2212 only or mostly in
10930589	SOD1	SOD1	5.1	it is reported to have a greater interaction with mutant SOD1 than with wildtype SOD1 7
10930589	SOD1	SOD1	5.1	have a greater interaction with mutant SOD1 than with wildtype SOD1 7
10930589	SOD1	SOD1	5.1	hypothesis of increased H 2 O 2 generation by mutant SOD1
10930589	SOD1	SOD1	5.1	has shown that DDC reacts with Cu(II) Cu II of SOD1
10930589	SOD1	SOD1	5.1	The reaction of DDC with SOD1 was shown to occur in two phases
10930589	SOD1	SOD1	5.1	a modest concentration of DDC (0.1_amp_#x2013;1.0 0.1_amp_#x2013 1.0 mM and SOD1 retains its full dismutase activity 19
10930589	SOD1	SOD1	5.1	Phase 2 involves displacement of Cu(II) Cu II from SOD1
10930589	SOD1	SOD1	5.1	Cu(II) Cu II polymerize into colloidal particles stabilized by unfolded SOD1 protein subunits
10930589	SOD1	SOD1	5.1	equal to 10 mM and leads to a loss of SOD1 dismutase activity 19
10930589	SOD1	SOD1	5.1	The contribution of SOD1 to C-DCF fluorescence in our studies was demonstrated by using
10930589	SOD1	SOD1	5.1	Fig 3A and B suggests that hydrogen peroxide generated by SOD1 was indeed involved in the oxidation of C-DCDHF
10930589	SOD1	SOD1	5.1	cells suggesting either altered interaction or modified stoichiometry between mutant SOD1 and DDC
10930589	SOD1	SOD1	5.1	2 O 2 damage due to increased concentrations of mutant SOD1 in these cells
10930589	SOD1	SOD1	5.1	Such an accumulation of mutant SOD1 has been reported in FALS spinal cords 33 and could
11396274	SOD1	SOD1	1.2	Neurochemistry of SOD1 and familial amyotrophic lateral sclerosis
11513882	SOD1	SOD1	6.0	lateral sclerosis (fALS) fALS are linked to mutations in the SOD1 gene which encodes the copper/zinc copper zinc superoxide dismutase (CuZnSOD)
11513882	SOD	SOD	4.3	monitored calcineurin activity in the presence of mutant and wild-type SOD
11513882	SOD	SOD	4.3	the degree of protection against inactivation of calcineurin by different SOD mutants correlates with the severity of the phenotype associated with
11513882	SOD1	SOD1	6.0	with the different mutations suggesting a potential role for calcineurin_amp_#x2013 SOD1 interaction in the etiology of fALS
11513882	SOD1	SOD1	6.0	Mutations in the SOD1 gene which encodes the enzyme copper/zinc copper zinc superoxide dismutase
11513882	SOD1	SOD1	6.0	Today more than 70 different mutations of the SOD1 gene are known ranging from mutations that are associated with
11513882	SOD1	SOD1	6.0	Recently it was shown that SOD1 protects calcineurin a serine/threonine-specific serine threonine-specific calcium/calmodulin-dependent calcium calmodulin-dependent phosphoprotein
11513882	SOD1	SOD1	6.0	the last years the primary molecular targets of the mutated SOD1 in fALS are still unknown
11513882	SOD	SODs	2.2	In this study we report that the mutant SODs were significantly less protective against calcineurin inactivation and that the
11513882	SOD	SODs	2.2	Wt and mutant SODs were purified and demetalated by Ni-NTA-affinity chromatography using imidazole (500
11513882	SOD	SOD	4.3	SOD assay and activity staining
11513882	SOD	SOD	4.3	For atomic emission spectrometry (AES), AES SOD proteins were washed five times in refolding buffer (Centrex Centrex
11513882	SOD	SOD	4.3	okadaic acid (5 5 _amp_#x3bc m 200 _amp_#x3bc g of SOD proteins and water ad 40 _amp_#x3bc l
11513882	SOD1	SOD1	6.0	test the hypothesis that calcineurin is a target of mutated SOD1 we used recombinant wt enzyme and three variants associated with
11513882	SOD	SOD	4.3	native electropherograms with NBT showed a corresponding pattern with wt SOD showing the highest activity followed by the D90A mutant whereas
11513882	SOD	SODs	2.2	conveyed the most protection of calcineurin activity of the mutant SODs studied
11513882	SOD	SOD	4.3	loss of over 60% of the protection confered by wt SOD
11513882	SOD	SOD	4.3	This effect was not due to reduced SOD activity of the mutant SODs compared to wt when the
11513882	SOD	SODs	2.2	was not due to reduced SOD activity of the mutant SODs compared to wt when the amounts of wt or mutant
11513882	SOD	SOD	4.3	compared to wt when the amounts of wt or mutant SOD were quadrupled (800 800 ng the loss of protection of
11513882	SOD	SOD	4.3	calcineurin activity was magnified rather than reduced for the fALS SOD mutants ( Fig 2b dark bars however the differences in
11513882	SOD	SOD	4.3	While wt SOD maintained its protective effect on calcineurin activity and co-incubation of
11513882	SOD	SODs	2.2	effect on calcineurin activity and co-incubation of calcineurin with the SODs associated with benign (D9OA) D9OA and classic (G93A) G93A fALS
11513882	SOD	SOD	4.3	only showed a slight reduction compared to 200 ng of SOD the SOD associated with the most severe form of fALS
11513882	SOD	SOD	4.3	a slight reduction compared to 200 ng of SOD the SOD associated with the most severe form of fALS (A4V) A4V
11513882	SOD	hSOD	2.2	activity meaning that over 80% of the protection of wt hSOD were lost due to this mutation
11513882	SOD	SOD	4.3	To address the observation that increased amounts of mutant SOD compounded the loss of calcineurin activity we tested a mixture
11513882	SOD	SODs	2.2	Our results thus demonstrate that mutant SODs can reduce the protection conferred by wt SOD
11513882	SOD	SOD	4.3	that mutant SODs can reduce the protection conferred by wt SOD
11513882	SOD1	SOD1	6.0	This observation supports the hypothesis that the SOD1 mutations found in fALS result in a negative gain of
11513882	SOD	SOD	4.3	in a reduction of the protection of calcineurin by wt SOD
11513882	SOD	SOD	4.3	How the different mutations in the ubiquitously expressed enzyme SOD cause the highly specific neuropathological phenotype associated with fALS remains
11513882	SOD	SOD	4.3	CuZnSOD 5 which itself accounts for 2% of brain protein SOD and calcineurin are both among the most abundant proteins in
11513882	SOD	SODs	2.2	In this study we report that mutated SODs loose their capacity to protect calcineurin from oxidative inactivation as
11513882	SOD	SOD	4.3	The SOD mutant showing the least protective effect (A4V) A4V is associated
11513882	SOD1	SOD1	6.0	reduced calcineurin activity in human neuroblastoma cells transfected with mutated SOD1 and in the forebrains of fALS-transgenic mice 9
11513882	SOD	SOD	4.3	Moreover when the amount of SOD protein was quadrupled in the assay the wt maintained its
11513882	SOD	SOD	4.3	the wt CuZnSOD protein and not simply the presence of SOD activity is needed for the protection of calcineurin from oxidative
11513882	SOD	SOD-generated	2.2	that the increased inactivation of calcineurin is mediated by mutated SOD-generated oxidative species different from superoxide a hypothesis that has already
11513882	SOD	SOD	4.3	be in accordance with the notion that overexpression of wt SOD together with fALS-associated SOD is not protective 21 an observation
11513882	SOD	SOD	4.3	the notion that overexpression of wt SOD together with fALS-associated SOD is not protective 21 an observation that is strengthened by
11513882	SOD	SODs	2.2	by the fact that a mixture of wt and mutant SODs only confers an intermediate rate of protection
11513882	SOD	SOD	4.3	The partial protective effect of wt SOD when mixed with mutant SOD may be explained by the
11513882	SOD	SOD	4.3	partial protective effect of wt SOD when mixed with mutant SOD may be explained by the necessity of SOD to bind
11513882	SOD	SOD	4.3	with mutant SOD may be explained by the necessity of SOD to bind to calcineurin to exert its protective effect
11513882	SOD	SODs	2.2	Wt and mutant SODs therefore would compete for binding to calcineurin so that part
11513882	SOD	SOD	4.3	of the calcineurin molecules still could be protected by wt SOD
11513882	SOD1	SOD1	6.0	It has to be noted however that the recombinant reconstituted SOD1 proteins used in this study show an abnormal zinc content
11513882	SOD1	SOD1	6.0	A reduced affinity of SOD1 mutants for zinc is an observation that has already been
11513882	SOD1	SOD1	6.0	However our wt SOD1 gives exactly the same rate of protection as SOD1 purified
11513882	SOD1	SOD1	6.0	wt SOD1 gives exactly the same rate of protection as SOD1 purified from erythrocytes and the D90A mutation which shows a
11513882	SOD	SODs	2.2	of our results a reduction of calcineurin activity by mutant SODs would therefore lead to prolonged NMDA receptor-channel openings and therefore
11513882	SOD1	SOD1	6.0	This would explain why glutamate potentiates the toxicity of mutant SOD1 in motor neurons 22
11513882	SOD	SODs	2.2	systems and a higher Ca content in cells expressing mutant SODs or in mutant SOD1 transgenic mice has been observed 23
11513882	SOD1	SOD1	6.0	Ca content in cells expressing mutant SODs or in mutant SOD1 transgenic mice has been observed 23 24 and 25 a
11513882	SOD1	SOD1	6.0	Characterization of the SOD1 proteins
11513882	SOD1	SOD1	6.0	The recombinant SOD1 proteins are characterized by a reduced activity and a reduced
11513882	SOD1	SOD1	6.0	Lower panel Activity staining of recombinant SOD1 proteins
11513882	SOD	SOD	4.3	activity can be preserved by addition of erythrocyte (ery) ery SOD or recombinant human (hr) hr SOD
11513882	SOD	SOD	4.3	of erythrocyte (ery) ery SOD or recombinant human (hr) hr SOD
11513882	SOD	SODs	2.2	Recombinant mutant SODs associated with fALS are less protective
11513882	SOD	SODs	2.2	Addition of quadruple amounts of wt or mutant SODs (black black bars reduces the protective ability of the mutants
11513882	SOD	SOD	4.3	n =6 * P _amp_#x3c 0.05 significantly different from wt SOD by Student_amp_#x2019 s t -test ** P _amp_#x3c 0.01 significantly
11513882	SOD	SOD	4.3	t -test ** P _amp_#x3c 0.01 significantly different from wt SOD by Student_amp_#x2019 s t -test
11513882	SOD	SODs	2.2	A mixture of wt and mutant SODs confers intermediate protection
11513882	SOD	SOD	4.3	Addition of wt SOD (400 400 ng to mutant SOD1s (400 400 ng results
11513882	SOD1	SOD1s	2.2	Addition of wt SOD (400 400 ng to mutant SOD1s (400 400 ng results in intermediate protective ability against oxidative
11513882	SOD	SOD	4.3	n =4 ** P _amp_#x3c 0.01 significantly different from mutant SOD alone by Student_amp_#x2019 s t -test
11679167	SOD	SODs	1.9	glucose consuming cultures some of the antioxidant defences such as SODs catalases and peroxidases are present at a very low level
11679167	SOD	SOD	1.9	been utilised for ALS research on clarifying the role of SOD mutations
11679167	SOD1	SOD1	1.9	the use of S cerevisiae in elucidating the mechanism of SOD1 mediated disease
11701756	SOD1	SOD1	0.9	mutations of the antioxidant enzyme Cu Zn superoxide dismutase (SOD1), SOD1 namely in neuroblastoma cells expressing either SOD1 mutant G93A or
11701756	SOD1	SOD1	0.9	superoxide dismutase (SOD1), SOD1 namely in neuroblastoma cells expressing either SOD1 mutant G93A or mutant H46R and in brain areas from
11701756	SOD1	SOD1	0.9	In this work we report that while wild-type SOD1 has a protective effect calcineurin is oxidatively inactivated by mutant
11701756	SOD1	SOD1s	0.9	has a protective effect calcineurin is oxidatively inactivated by mutant SOD1s in vitro this inactivation is mediated by reactive oxygen species
11701756	SOD1	SOD1s	0.9	These findings demonstrate that both wild-type and mutant SOD1s can interfere directly with calcineurin activity and further support the
11796206	SOD1	sod1	1.9	one fifth of these cases are associated with mutations in sod1 the gene that encodes human CuZnSOD 1
11796206	SOD	SOD	1.9	severe motor neuron degenerative syndrome despite normal or above normal SOD activities 2 3 4 and 5 whereas neither transgenic mice
11796206	SOD	SOD	1.9	because in vitro remetallation may not reflect the state of SOD mutants in vivo we developed a yeast model system to
11796206	SOD1	SOD-1	1.9	Yeast strains expressing the human SOD-1 mutant genes (G93A, G93A G93C A4V and L38V or the
11796206	SOD1	SOD1	1.9	were placed under the control of the wild type yeast SOD1 promoter and inserted into the high copy yeast/ yeast E
11796206	SOD1	sod1	1.9	plasmid was transformed into the Saccharomyces cerevisiae strain EG118 ( sod1 _amp_#x2212 which lacks the CuZnSOD polypeptide
11796206	SOD1	sod1	1.9	human and FALS mutant CuZnSOD proteins were expressed in an sod1 _amp_#x2212 strain of the yeast Saccharomyces cerevisiae in order to
11796206	SOD	SOD	1.9	of expression of the CuZnSOD proteins as well as the SOD activities of crude cytosol preparations were similar in the strains
11796206	SOD	SOD	1.9	those expressing FALS mutant CuZnSODs although slightly higher levels of SOD activity were sometimes found for the strains expressing the human
11796206	SOD	SOD	1.9	in the copper site of the enzyme and is fully SOD active 11 making it highly likely that the same situation
11905995	SOD1	SOD1-mediated	2.2	antioxidative activity or decreased oxygen free radical propagation prevent mutant SOD1-mediated motor neuron cell death and increase amyotrophic lateral sclerosis-like transgenic
11905995	SOD	SOD	2.2	neuron degeneration in transgenic mice overexpressing mutant superoxide dismutase (SOD)1 SOD 1 gene and mitochondrial abnormality is observed in human ALS
11905995	SOD1	SOD1	2.7	neuron-like cell death with mutant G93A-SOD1 but not with wild-type SOD1
11905995	SOD1	SOD1	2.7	transfection significantly increased NSC-34 motor neuron-like cell resistance to mutant SOD1
11905995	SOD1	SOD1-mediated	2.2	with spin trapping molecule 5' 5'-dimethylpryrroline-N-oxide (DMPO), DMPO prevented mutant SOD1-mediated mitochondrial dysfunction and cell death
11905995	SOD1	SOD1-mediated	2.2	suggest a causal relationship between enhanced oxidative stress and mutant SOD1-mediated motor neuron degeneration considering that enhanced oxygen free radical production
11905995	SOD1	SOD1	2.7	considering that enhanced oxygen free radical production results from the SOD1 structural alterations
12218958	SOD	SOD	1.9	Superoxide dismutase (SOD) SOD catalyzes the conversion of single electron reduced species of molecular
12218958	SOD	SOD	1.9	There are several classes of SOD that differ in their metal binding ability distribution in different
12218958	SOD1	SOD1	2.4	Among these Cu Zn superoxide dismutase (SOD1) SOD1 is widely distributed and comprises 90% of the total SOD
12218958	SOD	SOD	1.9	SOD1 is widely distributed and comprises 90% of the total SOD
12218958	SOD	SODs	1.9	The present review describes the role of SODs especially Cu Zn SOD in several diseases such as familial
12218958	SOD	SOD	1.9	present review describes the role of SODs especially Cu Zn SOD in several diseases such as familial amyotrophic lateral sclerosis (FALS),
12218958	SOD1	SOD1	2.4	Mutations in the SOD1 gene cause a familial form of amyotrophic lateral sclerosis
12218958	SOD1	SOD1	2.4	The mechanism by which mutant SOD1 causes the degeneration of motor neurons is not well understood
12218958	SOD1	SOD1s	1.9	Transgenic mice expressing multiple copies of FALS-mutant SOD1s develop an ALS-like motor neuron disease
12218958	SOD1	SOD1	2.4	Various observations and conclusions linking mutant SOD1 and FALS are discussed in this review in detail
12368231	SOD1	SOD1	1.2	Overexpression of SOD1 protects vulnerable motor neurons after spinal cord injury by attenuating
12368231	SOD1	SOD1	1.2	Defective Cu Zn-superoxide dismutase (SOD1) SOD1 is responsible for some types of amyotrophic lateral sclerosis and
12368231	SOD1	SOD1	1.2	mild spinal cord injury (SCI); SCI however the involvement of SOD1 ROS and apoptosis in their death has not been clarified
12368231	SOD1	SOD1-overexpressing	1.2	Mild compression SCI was induced in SOD1-overexpressing transgenic rats and wild-type littermates
12368231	SOD1	SOD1	1.2	apoptotic VMN death after SCI and that increased levels of SOD1 in VMN reduce oxidative stress thereby attenuating the activation of
12392777	SOD1	SOD-1	2.4	in the brain include Cu/Zn Cu Zn superoxide dismutase (SOD-1) SOD-1 and Mn superoxide dismutase (SOD-2) SOD-2 which catalyze the conversion
12437573	SOD1	SOD1	1.2	in human neuroblastoma cells expressing Cu Zn superoxide dismutase (SOD1) SOD1 mutant G93A and in brain areas from G93A transgenic mice
12437573	SOD1	SOD1	1.2	the possibility that by interfering directly with calcineurin activity mutant SOD1 can modulate pathways of signal transduction mediated by redox-sensitive transcription
12654515	SOD1	SOD1	3.7	The increased oxidative stress induced by mutant SOD1 is associated with motor neuron degeneration in both human ALS
12654515	SOD1	SOD1	3.7	degeneration in both human ALS and transgenic mice expressing mutant SOD1
12654515	SOD1	SOD1-mediated	1.7	The potential role of VEGF in preventing mutant SOD1-mediated motor neuron cell death was examined using a mouse NSC34
12654515	SOD1	SOD1	3.7	adenovirus containing mutant G93A-SOD1 but not vector control or wild-type SOD1 increased cellular oxidative stress and motor neuron-like cell death
12654515	SOD1	SOD1	3.7	discovery that mutations of the copper_amp_#x2013 zinc superoxide dismutase (SOD1) SOD1 gene cause a portion of human familial ALS and that
12654515	SOD1	SOD1	3.7	human familial ALS and that transgenic animal models expressing mutant SOD1 mimic human ALS have contributed significantly to our understanding of
12654515	SOD1	SOD1	3.7	The G93A mutation in SOD1 (G93A-SOD1) G93A-SOD1 is one of the 90 currently known mutations
12654515	SOD1	SOD1-mediated	1.7	Nevertheless effective approaches to prevent mutant SOD1-mediated motor neuron death remain largely unidentified
12654515	SOD1	SOD1	3.7	potential role of VEGF in motor neuron survival by mutant SOD1 effects remains largely unknown
12654515	SOD1	SOD1-mediated	1.7	cell culture model to test whether VEGF can prevent mutant SOD1-mediated motor neuron degeneration
12654515	SOD1	SOD1	3.7	Polyclonal antibody against SOD1 was purchased from Chemicon International (Temecula, Temecula CA USA
12654515	SOD1	SOD1-mediated	1.7	oxidative stress appears to be an early event of mutant SOD1-mediated motor neuron degeneration although the causal relationships between mutant SOD1-mediated
12654515	SOD1	SOD1-mediated	1.7	SOD1-mediated motor neuron degeneration although the causal relationships between mutant SOD1-mediated oxidative stress and mutant SOD1-mediated motor neuron death are not
12654515	SOD1	SOD1-mediated	1.7	the causal relationships between mutant SOD1-mediated oxidative stress and mutant SOD1-mediated motor neuron death are not fully elucidated
12654515	SOD1	SOD1	3.7	Infection with adenovirus containing human wild-type SOD1 (WT-SOD1) WT-SOD1 and human mutant G93A-SOD1 (G93A-SOD1) G93A-SOD1 increased target
12654515	SOD1	SOD1-	1.7	VEGF protects from mutant SOD1- TNF-_amp_#x3b1;- and H 2 O 2 -mediated mouse NSC34 motor
12654515	SOD1	mSOD1	1.7	with significant increases in cell survival in the presence of mSOD1 TNF-_amp_#x3b1 and hydrogen peroxide ( Fig 2 3.3
12654515	SOD1	SOD1	3.7	NSC34 motor neuron-like cell survival in the presence of mutant SOD1
12654515	SOD1	SOD1-mediated	1.7	of Akt by VEGF contributes to the protection from mutant SOD1-mediated motor neuron-like cell death
12654515	SOD1	SOD1	3.7	NSC34 motor neuron-like cell death associated with expression of mutant SOD1 4
12654515	SOD1	SOD1-mediated	1.7	prompted us to examine the effects of VEGF on mutant SOD1-mediated motor neuron-like cell death (i) i VEGF acts as a
12654515	SOD1	SOD1	3.7	in a mouse model 40 and (iv) iv mutations of SOD1 result in enhanced oxidative stress and contribute at least partially
12654515	SOD1	SOD1-induced	1.7	such an hypothesis whereby VEGF is effective in preventing mutant SOD1-induced mouse NSC34 motor neuron-like cell death
12654515	SOD1	SOD1	3.7	promotes motor neuron-like cell survival in the presence of mutant SOD1 thereby supporting the notion that deficits in VEGF protein induction
12654515	SOD1	SOD1	3.7	intrinsic characteristics of the neurotoxic initiators (glutamate glutamate vs mutant SOD1 leading to heterogeneities in downstream kinase recruitment and regulation
12654515	SOD1	SOD1-mediated	1.7	while the expression of constitutively active Akt partially prevented mutant SOD1-mediated motor neuron-like cell death even in the absence of VEGF
12654515	SOD1	SOD1-infected	1.7	apoptosis-related targets are specifically repressed by VEGF in the mutant SOD1-infected NSC34 motor neuron-like system
12654515	SOD1	SOD1	3.7	promote motor neuron-like cell survival in the presence of mutant SOD1
12654515	SOD1	SOD1-mediated	1.7	Fig 4 the long-lasting protective function of VEGF on mutant SOD1-mediated motor neuron-like cell death may be due to the modulation
12654515	SOD1	SOD1-	1.7	summary we have shown that VEGF can protect from mutant SOD1- and oxidative stress-mediated motor neuron-like cell death in a cell
12654515	SOD1	mSOD1	1.7	Expression of mutant G93A-SOD1 (mSOD1) mSOD1 increased NSC34 motor neuron-like cell death
12654515	SOD1	SOD1	3.7	(A) A Western analysis of SOD1 expression in NSC34 motor neuron-like cells
12654515	SOD1	mSOD1	1.7	(B) B Expression of mutant G93A-SOD1 (mSOD1) mSOD1 increased cellular production of reactive oxygen species
12654515	SOD1	SOD1-mediated	1.7	VEGF reduced hydrogen peroxide- TNF-_amp_#x3b1;- and mutant SOD1-mediated NSC34 motor neuron-like cell death
12663085	SOD1	SOD-1	2.7	Since mutations of the superoxide dismutase-1 (SOD-1) SOD-1 gene were first identified in 1993 it has been considered
12663085	SOD1	SOD-1	2.7	Bredesen advocated the possibility that SOD-1 even plays a role in sporadic ALS 7
12663085	SOD1	SOD-1	2.7	The glycation of SOD-1 under diabetic conditions has been studied extensively by Taniguchi et
12663085	SOD1	SOD-1	2.7	Glycation prompts the degradation of SOD-1 70
12663085	SOD1	SOD-1	2.7	the lens of diabetic rats glycation and the degradation of SOD-1 were clearly recognized 104
12663085	SOD1	SOD-1	2.7	Mutant SOD-1 is more easily glycated than normal SOD-1 and would therefore
12663085	SOD1	SOD-1	2.7	Mutant SOD-1 is more easily glycated than normal SOD-1 and would therefore be more rapidly degraded
12663085	SOD1	SOD-1	2.7	In addition mutant SOD-1 has a low affinity for copper
12663085	SOD1	SOD-1	2.7	Copper released from mutant or glycated SOD-1 would promote the generation of hydroxyl radicals by the Fenton
12663085	SOD1	SOD-1	2.7	Familial ALS and SOD-1
12663085	SOD1	SOD-1	2.7	evidence that more than 50 mutations in the gene for SOD-1 the cytosolic copper/zinc-binding copper zinc-binding dimeric form of a protective
12663085	SOD1	SOD-1	2.7	A discussion of FALS with SOD-1 mutations is complicated because transgenic expression of different SOD-1 mutants
12663085	SOD1	SOD-1	2.7	with SOD-1 mutations is complicated because transgenic expression of different SOD-1 mutants in both mice and rats causes an ALS-like syndrome
12663085	SOD1	SOD-1	2.7	mice and rats causes an ALS-like syndrome independently of whether SOD-1 catalytic activity is changed
12663085	SOD1	SOD-1	2.7	These observations suggest that a novel gain-of-function effect of mutant SOD-1 may have a pathogenic role in FALS 33 and 85
12663085	SOD1	SOD-1	2.7	First an increase in the peroxidase activity of mutant SOD-1 leading to hydroxyl radical production was assumed while several authors
12663085	SOD1	SOD-1	2.7	argued against the copper-mediated theory of motor neuron degeneration in SOD-1 mutant mice 101
12663085	SOD1	SOD-1	2.7	Finally mutant SOD-1 has a tendency to form aggregates spontaneously 31 and 89
12663085	SOD1	SOD-1	2.7	phosphorylated neurofilament protein are the characteristic markers of FALS with SOD-1 mutations
12663085	SOD1	SOD-1	2.7	Shibata et al 83 demonstrated the presence of intense SOD-1 immunoreactivity in the NHIs of FALS patients with a heterozygous
12663085	SOD1	SOD-1	2.7	to Val substitution at codon 4 (Ala4Val) Ala4Val in the SOD-1 gene
12663085	SOD1	SOD-1	2.7	Of added interest is a recent report that mutant SOD-1 expressed in cultured cells abnormally aggregates in the cytoplasm 12.1.3
12663085	SOD1	SOD-1	2.7	heterozygous Ala to Val substitution at codon 4 in the SOD-1 gene 83
12663085	SOD1	SOD-1	2.7	No focal collection of either CML or SOD-1 was found in neurons of the controls
12663085	SOD1	SOD-1	2.7	In the light of evidence that SOD-1 is a protein that is susceptible to the Maillard reaction
12663085	SOD1	SOD-1	2.7	Maillard reaction the finding of the coexistence of CML and SOD-1 in NHIs points to the possibility that CML-modified SOD-1 is
12663085	SOD1	SOD-1	2.7	and SOD-1 in NHIs points to the possibility that CML-modified SOD-1 is deposited in NHIs
12663085	SOD1	SOD-1	2.7	with familial ALS have been shown to contain not only SOD-1 but also phosphorylated NFP and ubiquitin
12663085	SOD1	SOD-1	2.7	The decreased activity of SOD-1 by glycation is not necessarily considered to be the sole
12663085	SOD	SOD-1-positive	1.4	Kato et al 35 and 37 found SOD-1-positive inclusions in astrocytes (astrocytic astrocytic hyaline inclusions or AHIs as
12663085	SOD1	SOD-1	2.7	as in neurons (NHIs) NHIs in patients with FALS with SOD-1 mutations and in transgenic mice expressing human SOD-1 with the
12663085	SOD1	SOD-1	2.7	FALS with SOD-1 mutations and in transgenic mice expressing human SOD-1 with the G85R mutation
12663085	SOD1	SOD-1	2.7	conducted in the spinal cords of FALS patients with the SOD-1 mutation (A4V) A4V in sporadic ALS patients and in age-matched
12663085	SOD	SOD-1-related	1.4	of pyrraline and imidazolone supports the non-oxidative mechanism in the SOD-1-related degeneration of motor neurons
12663085	SOD1	SOD-1	2.7	found that AGE-R1 immunoreactivity was co-localized with those of AGE SOD-1 and neurofilaments 12.7
12663085	SOD	SOD	1.7	SOD and catalase activities were not changed suggesting that specific defects
12684448	SOD	SOD	2.2	sclerosis ROS glutamate excitotoxicity glutamate transport cell culture free radicals SOD nitrotyrosine AMPA
12684448	SOD1	SOD1	2.2	linked to mutations in the enzyme superoxide dismutase 1 (SOD1) SOD1 (Rosen Rosen et al. 1993 the vast majority (90-95%) 90-95%
12684448	SOD1	SOD1	2.2	For spinal cord immunohistochemical studies SOD1 G93A transgenic mice (The The Jackson Laboratory Bar Harbor ME
12684448	SOD1	SOD1	2.2	For SOD1 G93A transgenic mouse studies spinal cords were removed from 90-
12684448	SOD	SOD	2.2	(MK-801)] MK-801 alone or in the presence of antioxidants (SOD, SOD 100 U/ml; U ml catalase 400 U/ml), U ml followed
12684448	SOD	SOD	2.2	seen in an annular pattern immediately surrounding MNs in the SOD mouse model of ALS is novel and lends support to
12684448	SOD	SOD	2.2	observed block of this oxidation by an extracellular antioxidant (SOD) SOD provides strong support for the idea that the ROS passes
12684448	SOD	SOD	2.2	In studies of glutamate transporters in ALS and SOD mutant mouse models there has been discussion as to whether
12684448	SOD	SOD	2.2	motor neurons and ventral horn in ALS and/or and or SOD mutant mouse models (Abe Abe et al. 1995 Beal et
12684448	SOD	SOD	2.2	increased nitrotyrosine staining in an annular pattern around MNs in SOD mutant mice suggest that this species may be involved
12684448	SOD1	SOD1	2.2	a critical involvement of both cell types in the mutant SOD1 mouse models of ALS development of disease seems to require
12684448	SOD	SOD	2.2	compatible with a multiplicity of inciting mechanisms (e.g., e.g. mutant SOD leading into a common self-propagating disease pathway
12684448	SOD	SOD	2.2	MK-801 alone ( left or with addition of the antioxidant SOD (100 100 U/ml) U ml to the bath (+ AO
12684448	SOD	SOD	2.2	both the absence ( black or presence ( white of SOD with minimal response in other neurons ( squares
12684448	SOD	SOD	2.2	( bottom left or presence ( bottom right of extracellular SOD (+ AO
12684448	SOD	SOD	2.2	micro M MK-801 alone or with addition of the antioxidants SOD (100 100 U/ml) U ml and catalase (400 400 U/ml)
12684448	SOD1	SOD1	2.2	Lumbar spinal cord sections from 3-month-old SOD1 transgenic mice ( G93A and nontransgenic controls ( non-TG (
12684448	SOD	SOD	2.2	With the addition of a cell-impermeant antioxidant enzyme (SOD, SOD 100 U/ml), U ml despite closely matched MN Delta F
12684448	SOD	SOD	2.2	This selective effect of extracellular SOD on astrocytic responses suggests strongly that the ROS generated in
12684448	SOD	SOD	2.2	extracellular bath (in in which it can be quenched by SOD before inducing oxidation in neighboring glia
12684448	SOD	SOD	2.2	uptake was prevented by addition of cell-impermeant antioxidant enzymes (SOD, SOD 100 U/ml; U ml catalase 400 U/ml) U ml to
12684448	SOD1	SOD1	2.2	use of transgenic mice expressing the G93A mutant form of SOD1 associated with familial forms of ALS (Gurney Gurney et al.
12718737	SOD	SOD	1.7	Antioxidant enzymes such as superoxide dismutase (SOD), SOD catalase and glutathione peroxidase (GPx) GPx have demonstrated therapeutic efficacy
12718737	SOD	SOD	1.7	Most recently SOD mimetics small molecules which mimic the activity of endogenous superoxide
12753090	ALS	ALS	1.9	expressing a Cu Zn superoxide dismutase mutant involved in familial ALS
12753090	SOD	SOD	1.9	for nNOS as Cu Zn superoxide dismutase (Cu,Zn Cu Zn SOD degradation by proteasome was influenced neither by its mutation nor
12753090	SOD	SOD	1.9	these results confirm the pro-oxidant activity of G93A Cu Zn SOD mutant and at the same time suggest a cross-talk between
12893007	SOD1	SOD1	2.9	in the gene for Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 can be identified
12893007	SOD	SOD	2.9	with mutation in the gene encoding the superoxide dismutase (SOD SOD 1 protein ([ Rosen et al
12893007	SOD	SOD	2.9	Most of the mutation in SOD 1 protein occur outside the active site and produce only
12893007	SOD	SOD	2.9	SOD 1 is a Cu/Zn-binding Cu Zn-binding ubiquitous antioxidative enzyme that
12893007	SOD	SOD	2.9	Loss of function in mutant SOD 1 proposes that motor neurons injury occurs by direct toxic
12893007	SOD	SOD	2.9	Weakened affinity for copper in the mutant SOD with consequent leakage of copper which may produce competition between
12893007	SOD	SOD	2.9	consequent leakage of copper which may produce competition between mutant SOD and other copper and zinc binding protein resulting in diminished
12893007	SOD	SOD	2.9	mutations could cause an alteration in copper active site of SOD 1 ([ Deng et al
12893007	SOD	SOD	2.9	Such changes could allow potential toxic gain of mutant SOD 1 to react with various subsidiary activities including peroxidase activity
12893007	SOD	SOD	2.9	The wide active site channel of the mutant SOD 1 protein may enhance the access of peroxynitrite to the
12893007	SOD	SOD	2.9	Mutant SOD 1 A4V protein aggregation and accumulation in the anterior horns_amp_#x2019
12893007	SOD	SOD	2.9	The relationship between the oxidative stress SOD 1 aggregation and accumulation of specific advanced glycation end products
12901835	SOD1	SOD1	2.4	expression of mutant G93A copper/zinc copper zinc superoxide dismutase (SOD1), SOD1 associated with familial amyotrophic lateral sclerosis specifically causes a decrease
12901835	SOD1	SOD1	2.4	in human neuroblastoma SH-SY5Y cells compared to cells overexpressing wild-type SOD1 and untransfected cells
12901835	SOD1	SOD1	2.4	No large aggregates of human SOD1 are detectable under basal growth conditions in any of the
12901835	SOD1	SOD1-generated	1.9	Our findings indicate that mitochondrial homeostasis is affected by mutant SOD1-generated ROS independently from the formation of aggregates and that this
12901835	SOD1	SOD1	2.4	coding for the antioxidant enzyme Cu Zn superoxide dismutase (SOD1) SOD1 Siddique et al 1991 Deng et al 1993 and Rosen
12901835	SOD1	SOD1	2.4	SOD1 typically has an antioxidant function because it removes the superoxide
12901835	SOD1	sod1	2.4	However mutations in sod1 gene do not cause FALS through simple loss of dismutating
12901835	SOD1	SOD1s	1.9	et al 1993 several lines of evidence indicate that mutant SOD1s are responsible for the death of motor neurons through the
12901835	SOD1	SOD1	2.4	be responsible for the enhancement of the peroxidative activity of SOD1 as independently reported by two groups Wiedau-Pazos et al 1996
12901835	SOD1	SOD1s	1.9	The second hypothesis relies on the observation that misfolded mutant SOD1s might release their metal ions (copper copper and zinc and
12901835	SOD1	SOD1	2.4	In particular decrease of the copper-buffering properties of SOD1 Steinkuhler et al 1991 could result in an increase of
12901835	SOD1	SOD1s	1.9	It is not clear at present whether misfolded SOD1s would also bind copper ions and mediate increase in oxidative
12901835	SOD1	SOD1	2.4	neuron disease with mice devoid of the Copper Chaperone for SOD1 (CCS CCS _amp_#x2212;/_amp_#x2212;) _amp_#x2212 _amp_#x2212 does not rescue the phenotype
12901835	SOD1	SOD1	2.4	as the major culprit in oxidative stress induced by mutant SOD1 Bush 2002
12901835	SOD1	SOD1	2.4	The recent demonstration that a substantial amount of SOD1 (previously previously thought of as being exclusively a cytosolic enzyme
12901835	SOD1	SOD1-linked	1.9	reductase defects have been shown both in postmortem brains from SOD1-linked FALS patients Browne et al 1998 and in skeletal muscle
12901835	SOD1	SOD1	2.4	spinal motor neurons of transgenic mice carrying G93A mutant human SOD1 Warita et al 2001
12901835	SOD1	SOD1	2.4	by site-directed mutagenesis of the cDNA coding for that mutant SOD1 cloning in expression vectors and transfection of parental human neuroblastoma
12901835	SOD1	SOD1	2.4	using the Immun-blot kit from Bio-Rad with a polyclonal antihuman SOD1 antibody Steinkuhler et al 1991
12901835	SOD1	SOD1	2.4	for 2 h at 37_amp_#xb0 C with a monoclonal antimouse SOD1 antibody (Sigma) Sigma 1 300 and for 2 h at
12901835	SOD1	SOD1	2.4	0.05 in line with the well-known protective role of wild-type SOD1 overexpression against free radicals
12901835	SOD1	SOD1	2.4	Aggregation of mutant SOD1
12901835	SOD1	SOD1	2.4	It has been suggested that aggregation of misfolded mutant SOD1 contributes to neurodegeneration in FALS
12901835	SOD1	SOD1	2.4	However it is still debated whether SOD1 aggregates represent a cause a correlate or a consequence of
12901835	SOD1	SOD1	2.4	In all of our lines no large aggregates of human SOD1 are detectable after immunostaining in basal growth conditions ( Fig
12901835	SOD1	SOD1	2.4	localized in the cytoplasm and roughly paralleled the level of SOD1 expression being more intense in transfected cells than in control
12901835	SOD1	SOD1-positive	1.9	specifically inhibit the proteasome activity with lactacystin for 16 h SOD1-positive aggregates localize in the cytoplasm of 30_amp_#x2013 40% cells expressing
12901835	SOD1	SOD1s	1.9	localize in the cytoplasm of 30_amp_#x2013 40% cells expressing mutant SOD1s but not in control cells
12901835	SOD1	SOD1	2.4	is paralleled by the appearance of an insoluble fraction containing SOD1 in extracts from cells expressing mutant SOD1 as seen in
12901835	SOD1	SOD1	2.4	insoluble fraction containing SOD1 in extracts from cells expressing mutant SOD1 as seen in Western blot experiments where detergent-soluble and -insoluble
12901835	SOD1	SOD1	2.4	to demonstrate that human neuroblastoma SH-SY5Y cell lines carrying G93A SOD1 mutation possess remarkable biochemical abnormalities compared to control cells such
12901835	SOD1	SOD1	2.4	This provides evidence that G93A SOD1 mutation acts as a remarkable source of intracellular oxidative stress
12901835	SOD1	SOD1	2.4	and mitochondrial ultrastructural abnormalities were found in animal models carrying SOD1 mutations Wong et al 1995
12901835	SOD1	SOD1	2.4	be a direct consequence of the pro-oxidant activity of mutant SOD1 indeed the use of NAC promptly reverts both increase in
12901835	SOD1	SOD1	2.4	survival and motor performance in transgenic mice with a G93A SOD1 mutation Andreassen et al 2000
12901835	SOD1	SOD1	2.4	When we specifically inhibit the proteasome activity insoluble SOD1 aggregates localize in the cytoplasm of cells expressing mutant SOD1s
12901835	SOD1	SOD1s	1.9	SOD1 aggregates localize in the cytoplasm of cells expressing mutant SOD1s but not in control cells
12901835	SOD1	SOD1s	1.9	growth factor (NGF)-differentiated NGF -differentiated PC12 cells transfected with mutant SOD1s (SODMT, SODMT V148G or A4V
12901835	SOD1	SOD1	2.4	survey on the properties of a large number of mutant SOD1 in vitro Hayward et al 2002 and Rodriguez et al
12909279	SOD1	SOD1	2.7	coding for the antioxidant enzyme Cu Zn superoxide dismutase (SOD1) SOD1 have been reported in fALS patients 21 and 80
12909279	SOD1	SOD1	2.7	SOD1 is a very well-characterised homodimeric enzyme present in virtually every
12909279	SOD1	SOD1	2.7	SOD1 binds zinc and copper ions with the Cu atom playing
12909279	SOD1	SOD1	2.7	Linkage studies have revealed that mutations in SOD1 are responsible for 10_amp_#x2013 15% of fALS cases 40
12909279	SOD1	SOD1	2.7	To date there are about 100 different SOD1 point mutations ( www.als.org reported in fALS families with various
12909279	SOD1	SOD1	2.7	and result in alteration of amino acids scattered throughout the SOD1 structure while some mutations affect the active site others are
12909279	SOD1	SOD1s	1.9	For this reason the mechanisms through which expression of mutant SOD1s result in motoneuron injury and death are still controversial
12909279	SOD1	SOD1	2.7	believed that the gain of a novel toxic function of SOD1 is responsible for the acquisition of the pathological phenotype
12909279	SOD1	SOD1	2.7	SOD1 is an abundant component of many cell types accounting for
12909279	SOD1	SOD1	2.7	_amp_#x201c conformational_amp_#x201d diseases formation of insoluble aggregates of misfolded mutant SOD1 contributes to cell death in fALS
12909279	SOD1	SOD1	2.7	However it is still debated whether SOD1 aggregates represent a cause a correlate or a consequence of
12909279	SOD1	SOD1	2.7	of sALS patients contain cytoplasmic aggregates that show immunoreactivity for SOD1 and ubiquitin similar inclusion bodies were also observed in SOD1-linked
12909279	SOD1	SOD1-linked	2.2	SOD1 and ubiquitin similar inclusion bodies were also observed in SOD1-linked fALS patients 12
12909279	SOD1	SOD1	2.7	More recent evidence questioned the relevance of SOD1 aggregates in the pathogenesis of fALS
12909279	SOD1	SOD1	2.7	For instance it has been reported that formation of SOD1 aggregates is independent of induction of cell death 52 and
12909279	SOD1	SOD1	2.7	SOD1 aggregates may be toxic through sequestration of other proteins required
12909279	SOD1	SOD1	2.7	Also SOD1 aggregates may reduce proteasome activity needed for normal protein turnover
12909279	SOD1	SOD1s	1.9	How mutant SOD1s cause oxidative stress and which molecules represent direct targets/propagators targets
12909279	SOD1	SOD1	2.7	the active site could exacerbate the reported peroxidative activity of SOD1 as suggested by studies in vitro 100 and in vivo
12909279	SOD1	SOD1	2.7	it has been suggested that aggregated but still active mutant SOD1 may mediate the formation of ROS
12909279	SOD1	SOD1	2.7	uptake intracellular delivery from chaperones (e.g e.g copper chaperone for SOD1 (CCS), CCS COX17 and Atx1 to specific targets (such such
12909279	SOD1	SOD1	2.7	CCS COX17 and Atx1 to specific targets (such such as SOD1 and cytochrome c oxidase and/or and or storage in copper
12909279	SOD1	SOD1-linked	2.2	This is not the case in SOD1-linked fALS in which no alteration of total copper content is
12909279	SOD1	SOD1-linked	2.2	This may be occurring in SOD1-linked fALS since it is known that many mutant SOD1s do
12909279	SOD1	SOD1s	1.9	in SOD1-linked fALS since it is known that many mutant SOD1s do not bind metals properly in vitro and possibly in
12909279	SOD1	SOD1s	1.9	ability to bind copper (and and zinc among different mutant SOD1s have been reported 42 this seems to be to a
12909279	SOD1	SOD1	2.7	general characteristic of fALS-SOD1s reinforcing the previously suggested hypothesis that SOD1 plays a crucial role in copper buffering
12909279	SOD1	sod1	2.7	In man sod1 is present in a single copy per haploid genome and
12909279	SOD1	SOD1	2.7	penetrance close to 1 with patients usually heterozygous for mutant SOD1 except for some families carrying the mutation D90A
12909279	SOD1	SOD1	2.7	Therefore alteration of half of SOD1 molecules in patients may result in a relevant imbalance of
12909279	SOD1	SOD1	2.7	of either copper buffering or copper chemistry especially considering that SOD1 is a very abundant protein representing up to 1% of
12909279	SOD1	SOD1	2.7	models 16 and 32 inhibit the peroxidase activity of mutant SOD1 A4V and G93A in vitro 100 rescue elevation of ROS
12909279	SOD1	SOD1-linked	2.2	Cp has been described 68 that could be altered in SOD1-linked fALS because of copper mishandling and cause iron mishandling
12909279	SOD	SOD	1.9	yeast Saccharomyces cerevisiae 20 and 87 in which lack of SOD causes a substantial increase in the Fe demand of the
12909279	SOD	SOD-defective	1.9	The increased Fe demand of the SOD-defective yeast cell may reflect its aim to continuously reconstitute the
12909279	SOD1	SOD1	2.7	an imbalance in ROS production_amp_#x2014 either caused directly by mutant SOD1 or indirectly by other mechanisms_amp_#x2014 could be responsible for damage
12909279	SOD1	SOD1-linked	2.2	complexes has been reported in patients and in models for SOD1-linked fALS 19 49 60 61 and 101 and there is
12909279	SOD1	SOD1	2.7	that the metal-mediated free radical generation derived either from mutant SOD1 or from mishandled metal ions might be related to the
12909279	SOD1	SOD1-linked	2.2	clinically indistinguishable therefore studies on the less frequent genetically inherited SOD1-linked form of the disease are thought to be potentially useful
12909279	SOD1	SOD1	2.7	in order to understand cellular alterations induced by mutation of SOD1 17 and 48 up to date no study has shed
12909279	SOD1	SOD1	2.7	patients and in the transgenic mice model (while while mutant SOD1 is expressed ubiquitously
12909279	SOD1	SOD1	2.7	Therefore the neurotoxic effect of mutant SOD1 seems to be not a simple consequence of its expression
12909279	SOD1	SOD1	2.7	findings indicating that neuroinflammatory processes mediate the pathogenic effect of SOD1 mutation (and, and more in general ALS pathogenesis
12909279	SOD1	SOD1	2.7	the only (partially) partially understood is the presence of mutant SOD1
12909279	SOD1	SOD1	2.7	The general concept is that upon mutation SOD1 is partially misfolded and binds copper improperly
12909279	SOD	SOD-like	1.9	In both cases evidence of SOD-like activity arising from copper bound to peptide A_amp_#x3b2 and to
14572730	SOD	SOD	1.4	a mutant form of copper/zinc copper zinc superoxide dismutase (SOD) SOD 1 in patients with familial ALS which supports a crucial
14625013	SOD1	mSOD1	1.4	human mutated form (G93A) G93A of Cu Zn-superoxide dismutase (mSOD1) mSOD1 develop motor neuron degeneration resembling amyotrophic lateral sclerosis
14625013	SOD1	mSOD1	1.4	0.375 g/kg) g kg on disease onset and survival of mSOD1 transgenic mice
14625013	SOD1	mSOD1	1.4	We conclude that zinc sulfate amplifies the mSOD1 transgenic mouse phenotype
14625013	SOD1	SOD1	1.4	but mutations in the gene encoding Cu Zn-superoxide dismutase (SOD1) SOD1 are found in approximately 2% of ALS patients 12
14625013	SOD1	SOD1	1.4	Transgenic mice overexpressing human SOD1 carrying the G93A mutation (mSOD1) mSOD1 develop a rapidly progressive
14625013	SOD1	mSOD1	1.4	Transgenic mice overexpressing human SOD1 carrying the G93A mutation (mSOD1) mSOD1 develop a rapidly progressive muscular weakness due to motor neuron
14625013	SOD1	SOD1	1.4	SOD1 is a metalloenzyme that catalyzes the conversion of superoxide to
14625013	SOD1	mSOD1	1.4	Such gained properties of mSOD1 include increased formation of free radicals with hydrogen peroxide as
14625013	SOD1	SOD1	1.4	In vitro studies showed that mutations in SOD1 destabilize the protein and decrease the affinity of SOD1 for
14625013	SOD1	SOD1	1.4	in SOD1 destabilize the protein and decrease the affinity of SOD1 for zinc up to 50-fold compared to the wild type
14625013	SOD1	SOD1	1.4	Zinc-deficient SOD1 leads to an increase in nitrotyrosine formation and induces apoptosis
14625013	SOD1	SOD1	1.4	This toxicity required copper to be bound to SOD1 and was not present when SOD1 was replete with zinc
14625013	SOD1	SOD1	1.4	to be bound to SOD1 and was not present when SOD1 was replete with zinc 3
14625013	SOD1	mSOD1	1.4	upregulation of MT's is seen in the spinal cord of mSOD1 transgenic mice 11 and reduction of MT-I and -II significantly
14625013	SOD1	mSOD1	1.4	and reduction of MT-I and -II significantly reduces survival of mSOD1 transgenic mice 10
14625013	SOD1	SOD1	1.4	expression of MT's would be neuroprotective in transgenic high-copy human SOD1 G93A mice (Jackson Jackson Laboratory Bar Harbor MN
14625013	SOD1	SOD1	1.4	G93A male SOD1 mice were crossbred with non-transgenic Balb/C Balb C females
14625013	SOD1	SOD1	1.4	Prior to the G93A SOD1 experiment the effect of high dose zinc sulphate on hematological
14625013	SOD1	SOD1	1.4	In the G93A SOD1 mice the hind-paw extension reflex test was performed 5 days
14625013	SOD1	mSOD1	1.4	In untreated mSOD1 transgenic mice a similar though clearly more intense staining pattern
14625013	SOD1	mSOD1	1.4	in immunoreactivity for MT's were observed between zinc-treated and untreated mSOD1 transgenic mice ( Figs 2B C
14625013	SOD1	mSOD1	1.4	would attenuate motor neuron death and thus extend survival of mSOD1 transgenic mice
14625013	SOD1	mSOD1	1.4	zinc sulphate (0.375 0.375 g/kg) g kg decreased survival of mSOD1 transgenic mice
14625013	SOD1	mSOD1	1.4	level in the spinal cord of both treated and untreated mSOD1 transgenic mice but a further upregulation of MT in the
14625013	SOD1	mSOD1	1.4	The selective toxicity in mSOD1 transgenic mice may be due to enhanced motor neuron death
14625013	SOD1	mSOD1	1.4	raises two related questions why is zinc not neuroprotective in mSOD1 transgenic mice and why does it even appear to accelerate
14625013	SOD1	mSOD1	1.4	maximum in the spinal cord (and and intestinal wall of mSOD1 transgenic mice 11 so that a further upregulation cannot be
14625013	SOD1	mSOD1	1.4	direct toxic effect of zinc on motor neurons 18 of mSOD1 transgenic mice
14648077	SOD1	SOD1	7.9	developed both an antioxidant system containing superoxide dismutase 1 (SOD1) SOD1 and a redox system including peroxiredoxin2 (Prx2, Prx2 thioredoxin peroxidase
14648077	SOD1	SOD1	7.9	peroxiredoxin2 (Prx2, Prx2 thioredoxin peroxidase and glutathione peroxidase1 (GPx1): GPx1 SOD1 converts superoxide radicals into hydrogen peroxide (H H 2 O
14648077	SOD1	SOD1	7.9	the interaction of the redox system (Prx2/GPx1) Prx2 GPx1 with SOD1 in SOD1-mutated motor neurons in vivo we produced an affinity-purified
14648077	SOD1	SOD1-mutated	1.7	of the redox system (Prx2/GPx1) Prx2 GPx1 with SOD1 in SOD1-mutated motor neurons in vivo we produced an affinity-purified rabbit antibody
14648077	SOD1	SOD1	7.9	and an Ala Val substitution at codon 4 in the SOD1 gene as well as in transgenic rats expressing human SOD1
14648077	SOD1	SOD1	7.9	SOD1 gene as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations
14648077	SOD1	SOD1-mutated	1.7	The LBHIs in motor neurons from the SOD1-mutated FALS patients and transgenic rats showed identical immunoreactivities for Prx2
14648077	SOD1	SOD1	7.9	In addition the localizations of the immunoreactivities for SOD1 and Prx2/GPx1 Prx2 GPx1 were similar in the inclusions the
14648077	SOD1	SOD1	7.9	in the inclusions the co-aggregation of Prx2/GPx1 Prx2 GPx1 with SOD1 in neuronal LBHIs in mutant SOD1-related FALS patients and transgenic
14648077	SOD1	SOD1-related	1.7	Prx2/GPx1 Prx2 GPx1 with SOD1 in neuronal LBHIs in mutant SOD1-related FALS patients and transgenic rats was evident
14648077	SOD1	SOD1	7.9	the redox system such co-aggregation of Prx2/GPx1 Prx2 GPx1 with SOD1 in neuronal LBHIs may lead to the breakdown of the
14648077	SOD1	SOD1-mediated	1.7	breakdown of the redox system itself thereby amplifying the mutant SOD1-mediated toxicity in mutant SOD1-linked FALS patients and transgenic rats expressing
14648077	SOD1	SOD1-linked	1.7	system itself thereby amplifying the mutant SOD1-mediated toxicity in mutant SOD1-linked FALS patients and transgenic rats expressing human mutant SOD1
14648077	SOD1	SOD1	7.9	mutant SOD1-linked FALS patients and transgenic rats expressing human mutant SOD1
14648077	SOD	SOD	1.7	first antioxidant enzyme group three isoforms of superoxide dismutase (SOD) SOD EC 1.15.1.1 have been identified SOD1 SOD2 and SOD3 9
14648077	SOD1	SOD1	7.9	of superoxide dismutase (SOD) SOD EC 1.15.1.1 have been identified SOD1 SOD2 and SOD3 9
14648077	SOD	SOD	1.7	Unlike SOD and catalase enzymes of the Prx and GPx families require
14648077	SOD1	SOD1	7.9	amyotrophic lateral sclerosis (FALS) FALS are caused by a mutant SOD1 15 17 18
14648077	SOD1	SOD1	7.9	SOD1 is thought to be an essential component of neuronal Lewy
14648077	SOD1	SOD1-mutated	1.7	LBHIs in affected anterior horn cells are morphological hallmarks of SOD1-mutated motor neurons of FALS patients 3 11 12 13 14
14648077	SOD1	SOD1-mutated	1.7	To cope with destructive ROSs even SOD1-mutated motor neurons induce mutant and wild-type SOD1 as well as
14648077	SOD1	SOD1	7.9	destructive ROSs even SOD1-mutated motor neurons induce mutant and wild-type SOD1 as well as Prx2 and GPx1
14648077	SOD1	SOD1	7.9	Considering that Prx2 and GPx1 interact not only with wild-type SOD1 but also with mutant SOD1 the interaction of Prx2/GPx1 Prx2
14648077	SOD1	SOD1	7.9	interact not only with wild-type SOD1 but also with mutant SOD1 the interaction of Prx2/GPx1 Prx2 GPx1 with SOD1 has been
14648077	SOD1	SOD1	7.9	with mutant SOD1 the interaction of Prx2/GPx1 Prx2 GPx1 with SOD1 has been suggested to contribute to mutant SOD1 aggregation toxicity
14648077	SOD1	SOD1	7.9	GPx1 with SOD1 has been suggested to contribute to mutant SOD1 aggregation toxicity Prx2/GPx1 Prx2 GPx1 possibly aggregate as LBHIs in
14648077	SOD1	SOD1-mutated	1.7	aggregation toxicity Prx2/GPx1 Prx2 GPx1 possibly aggregate as LBHIs in SOD1-mutated motor neurons
14648077	SOD1	SOD1-mediated	1.7	GPx1 might affect the intracytoplasmic redox regulation and amplify mutant SOD1-mediated toxicity
14648077	SOD1	SOD1	7.9	the interaction of Prx2/GPx1 Prx2 GPx1 (redox redox system with SOD1 in SOD1-mutated motor neurons in vivo we first produced an
14648077	SOD1	SOD1-mutated	1.7	of Prx2/GPx1 Prx2 GPx1 (redox redox system with SOD1 in SOD1-mutated motor neurons in vivo we first produced an antibody against
14648077	SOD1	SOD1-mutated	1.7	expressions of both Prx2 and GPx1 in neuronal LBHIs in SOD1-mutated motor neurons of humans and animal models
14648077	SOD1	SOD1	7.9	SOD1 analysis revealed that the members of the Japanese Oki family
14648077	SOD	SOD	1.7	of five FALS cases ( FALS familial amyotrophic lateral sclerosis SOD superoxide dismutase LBHI Lewy body-like hyaline inclusion 2-bp two-base pair
14648077	SOD1	SOD1	7.9	transgenic line (H46R-4) H46R-4 in which the level of human SOD1 with the H46R mutation was 6 times the level of
14648077	SOD1	SOD1	7.9	was 6 times the level of that of endogenous rat SOD1 27
14648077	SOD1	SOD1	7.9	transgenic line (G93A-39) G93A-39 in which the level of human SOD1 with the G93A mutation was 2.5 times the level of
14648077	SOD1	SOD1	7.9	G93A mutation was 2.5 times the level of endogenous rat SOD1 27
14648077	SOD1	SOD1	7.9	BSA-PBS pH 7.4 2 and a polyclonal antibody to human SOD1 (diluted diluted 1 10 000 in 1% BSA-PBS pH 7.4
14648077	SOD1	SOD1-linked	1.7	In mutant SOD1-linked FALS patients the neuronal LBHIs were generally composed of eosinophilic
14648077	SOD1	SOD1	7.9	C family and the transgenic rats expressing two different human SOD1 mutations (H46R H46R and G93A were intensely immunostained by the
14648077	SOD1	SOD1	7.9	and G93A were intensely immunostained by the antibody against human SOD1 (Figs Figs 4 A D 5 A D 6 A
14648077	SOD1	SOD1	7.9	many intracytoplasmic and intraneuritic LBHIs was similar to that of SOD1 in both diseases
14648077	SOD1	SOD1	7.9	Prx2 the immunolocalization of GPx1 was similar to that of SOD1 in both diseases
14648077	SOD1	SOD1	7.9	an FALS patient with a two-base pair deletion in the SOD1 gene
14648077	SOD1	SOD1	7.9	A Immunostaining for SOD1 immunoreactivity is mostly restricted to the halo
14648077	SOD1	SOD1-positive	1.7	B Immunostaining for GPx1 immunoreactivity is located in the SOD1-positive portion of the LBHI
14648077	SOD1	SOD1	7.9	Co-localization of the three proteins SOD1 GPx1 and Prx2 in the LBHI is evident
14648077	SOD1	SOD1	7.9	core and halo-type LBHI in a transgenic rat expressing human SOD1 with an H46R mutation
14648077	SOD1	SOD1	7.9	Immunostaining for SOD1 ( D GPx1 ( E and Prx2 ( F
14648077	SOD1	SOD1	7.9	Similar stainability and immunolocalization of SOD1 GPx1 and Prx2 in the LBHI are observed ( LBHI
14648077	SOD1	SOD1	7.9	LBHI Lewy body-like hyaline inclusion FALS familial amyotrophic lateral sclerosis SOD1 superoxide dismutase 1 GPx1 glutathione peroxidase1 Prx2 peroxiredoxin2
14648077	SOD1	SOD1	7.9	LBHI in an FALS patient with an A4V mutation in SOD1 gene
14648077	SOD1	SOD1	7.9	Immunostaining for SOD1 ( A GPx1 ( B and Prx2 ( C
14648077	SOD1	SOD1	7.9	an FALS patient with a two-base pair deletion in the SOD1 gene
14648077	SOD1	SOD1	7.9	Immunostaining for SOD1 ( D GPx1 ( E and Prx2 ( F
14648077	SOD1	SOD1-positive	1.7	Prx2 ( F are observed in only part of the SOD1-positive LBHI
14648077	SOD1	SOD1	7.9	LBHI Lewy body-like hyaline inclusion FALS familial amyotrophic lateral sclerosis SOD1 superoxide dismutase 1 GPx1 glutathione peroxidase1 Prx2 peroxiredoxin2
14648077	SOD1	SOD1	7.9	the spinal anterior horn in a transgenic rat expressing human SOD1 with an H46R mutation immunostained with antibodies against SOD1 (
14648077	SOD1	SOD1	7.9	human SOD1 with an H46R mutation immunostained with antibodies against SOD1 ( A and Prx2 ( B
14648077	SOD1	SOD1	7.9	and sausage-like LBHIs in the neuropil are positive for both SOD1 and Prx2 ( arrows ( SOD1 superoxide dismutase1 LBHI Lewy
14648077	SOD1	SOD1	7.9	are positive for both SOD1 and Prx2 ( arrows ( SOD1 superoxide dismutase1 LBHI Lewy body-like hyaline inclusion Prx2 peroxiredoxin2
14648077	SOD1	SOD1	7.9	the spinal anterior horn in a transgenic rat expressing human SOD1 with an H46R mutation immunostained with antibodies against SOD1 (
14648077	SOD1	SOD1	7.9	human SOD1 with an H46R mutation immunostained with antibodies against SOD1 ( A and GPx1 ( B
14648077	SOD1	SOD1	7.9	Round LBHIs in the neuropil are positive for both SOD1 and GPx1 ( arrows ( SOD1 superoxide dismutase1 LBHI Lewy
14648077	SOD1	SOD1	7.9	are positive for both SOD1 and GPx1 ( arrows ( SOD1 superoxide dismutase1 LBHI Lewy body-like hyaline inclusion GPx1 glutathione peroxidase1
14648077	SOD1	SOD1	7.9	50 _amp_micro m Noticeably the co-localization of the three proteins SOD1 Prx2 and GPx1 in neuronal LBHIs in SOD1-mutated FALS patients
14648077	SOD1	SOD1-mutated	1.7	three proteins SOD1 Prx2 and GPx1 in neuronal LBHIs in SOD1-mutated FALS patients and transgenic rats (H46R H46R and G93A was
14648077	SOD1	SOD1-positive	1.7	E immunostaining was observed in only some areas of the SOD1-positive LBHIs
14648077	SOD1	SOD1	7.9	As expected 12 13 16 27 30 SOD1 protein (probably probably the mutant form was found to aggregate
14648077	SOD1	SOD1	7.9	anterior horn cells as neuronal LBHIs in FALS patients with SOD1 gene mutations and transgenic rats expressing human SOD1 with H46R
14648077	SOD1	SOD1	7.9	patients with SOD1 gene mutations and transgenic rats expressing human SOD1 with H46R and G93A mutations
14648077	SOD1	SOD1	7.9	Intense co-expression of SOD1 Prx2 and GPx1 in neuronal LBHIs in both diseases was
14648077	SOD1	SOD1-mutated	1.7	To eliminate ROSs SOD1-mutated motor neurons in mutant SOD1-linked FALS and transgenic rats (G46R
14648077	SOD1	SOD1-linked	1.7	To eliminate ROSs SOD1-mutated motor neurons in mutant SOD1-linked FALS and transgenic rats (G46R G46R and G93A induce mutant/wild-type
14648077	SOD1	SOD1	7.9	transgenic rats (G46R G46R and G93A induce mutant/wild-type mutant wild-type SOD1 as an antioxidant system and Prx2/GPx1 Prx2 GPx1 as a
14648077	SOD1	SOD1	7.9	In this in vivo milieu where mutant SOD1 exists Prx2 and GPx1 would aberrantly interact with the mutant
14648077	SOD1	SOD1	7.9	exists Prx2 and GPx1 would aberrantly interact with the mutant SOD1 which is assumed to aggregate easily by itself 8
14648077	SOD1	SOD1	7.9	Among the multiple theories of how mutant SOD1 contributes to motor neuron death in mutant SOD1-related FALS and
14648077	SOD1	SOD1-related	1.7	how mutant SOD1 contributes to motor neuron death in mutant SOD1-related FALS and transgenic animal models expressing human mutant SOD1 the
14648077	SOD1	SOD1	7.9	mutant SOD1-related FALS and transgenic animal models expressing human mutant SOD1 the aggregation of mutant SOD1 in neurons leads to part
14648077	SOD1	SOD1	7.9	animal models expressing human mutant SOD1 the aggregation of mutant SOD1 in neurons leads to part of the mutant SOD1-mediated toxicity
14648077	SOD1	SOD1-mediated	1.7	mutant SOD1 in neurons leads to part of the mutant SOD1-mediated toxicity through the formation of advanced glycation endproduct-modified SOD1 that
14648077	SOD1	SOD1	7.9	mutant SOD1-mediated toxicity through the formation of advanced glycation endproduct-modified SOD1 that is insoluble and cytotoxic 16
14648077	SOD1	SOD1	7.9	with a two-base pair deletion at codon 126 of the SOD1 gene (Oki Oki family and G85R transgenic mice has revealed
14648077	SOD1	SOD1	7.9	G85R transgenic mice has revealed that not only does mutant SOD1 provoke inclusion formation but that normal SOD1 also co-aggregates in
14648077	SOD1	SOD1	7.9	only does mutant SOD1 provoke inclusion formation but that normal SOD1 also co-aggregates in these inclusions 3
14648077	SOD1	SOD1	7.9	with the facts that there are neuronal LBHIs positive for SOD1 Prx2 and GPx1 in the milieu where mutant SOD1 exists
14648077	SOD1	SOD1	7.9	for SOD1 Prx2 and GPx1 in the milieu where mutant SOD1 exists but no LBHIs (no no aggregations exist under physiological
14648077	SOD1	SOD1	7.9	demonstrates an aberrant interaction of Prx2/GPx1 Prx2 GPx1 with mutant SOD1 the aggregation of which results in neuronal LBHIs
14648077	SOD1	SOD1	7.9	In addition intra-inclusional co-aggregation of Prx2/GPx1 Prx2 GPx1 with mutant SOD1 causes the intracytoplasmic reduction of Prx2/GPx1, Prx2 GPx1 thereby reducing
14648077	SOD	SOD	1.7	A similar aberrant interaction of the copper chaperone for SOD (CCS) CCS and SOD1 (probably probably CCS-mutant SOD1 also occurs
14648077	SOD1	SOD1	7.9	interaction of the copper chaperone for SOD (CCS) CCS and SOD1 (probably probably CCS-mutant SOD1 also occurs in the formation of
14648077	SOD1	SOD1	7.9	chaperone for SOD (CCS) CCS and SOD1 (probably probably CCS-mutant SOD1 also occurs in the formation of the neuronal LBHIs in
14648077	SOD1	SOD1-linked	1.7	occurs in the formation of the neuronal LBHIs in mutant SOD1-linked FALS 19 and the mutant SOD1 transgenic mouse model 32
14648077	SOD1	SOD1	7.9	neuronal LBHIs in mutant SOD1-linked FALS 19 and the mutant SOD1 transgenic mouse model 32
14648077	SOD1	SOD1	7.9	normal constitutive proteins with the aberrant interaction of cytotoxic mutant SOD1 with Prx2/GPx1 Prx2 GPx1 directly regulating a redox system our
14648077	SOD1	SOD1	7.9	speculate that not only co-aggregation of Prx2/GPx1 Prx2 GPx1 and SOD1 into LBHIs but also intracytoplasmic reduction of Prx2/GPx1 Prx2 GPx1
14648077	SOD1	SOD1-mutated	1.7	to the breakdown of the redox system itself in these SOD1-mutated neurons and this may be one of the endogenous mechanisms
14648077	SOD1	SOD1	7.9	whether this aberrant interaction of Prx2/GPx1 Prx2 GPx1 with mutant SOD1 is a direct or an indirect effect based on the
14648077	SOD1	SOD1-mutated	1.7	direct or an indirect effect based on the pathogenesis of SOD1-mutated FALS disease itself or whether Prx2 and GPx1 play a
14648077	SOD1	SOD1	7.9	GPx1 play a primary or a secondary role to mutant SOD1
14648077	SOD1	SOD1	7.9	the aberrant interaction and co-aggregation of Prx2/GPx1 Prx2 GPx1 and SOD1 (probably probably Prx2/GPx1 Prx2 GPx1 and mutant SOD1 in FALS
14648077	SOD1	SOD1	7.9	GPx1 and SOD1 (probably probably Prx2/GPx1 Prx2 GPx1 and mutant SOD1 in FALS patients with SOD1 gene mutations and transgenic rats
14648077	SOD1	SOD1	7.9	Prx2/GPx1 Prx2 GPx1 and mutant SOD1 in FALS patients with SOD1 gene mutations and transgenic rats expressing human SOD1 mutations may
14648077	SOD1	SOD1	7.9	patients with SOD1 gene mutations and transgenic rats expressing human SOD1 mutations may amplify a more marked mutant SOD1-mediated toxicity
14648077	SOD1	SOD1-mediated	1.7	expressing human SOD1 mutations may amplify a more marked mutant SOD1-mediated toxicity
14660707	SOD1	SOD1	1.1	inhibition are paralleled by observations in cell lines expressing mutant SOD1 which show increased basal Ca 2 loads ( Carri et
14660707	SOD1	SOD1	1.1	resemble increased Na currents and enhanced neuronal excitability in mutant SOD1 mouse spinal MNs ( Kuo et al 2002 2003
14660707	SOD1	SOD1	1.1	by a mutated Cu/Zn Cu Zn super oxide dismutase (SOD1) SOD1 is thought to be causally involved in MN degeneration (
14690536	SOD1	SOD1	2.7	Expression of SOD1 G93A or wild-type SOD1 in primary cultures of astrocytes down-regulates
14690536	SOD1	SOD1	2.7	Expression of SOD1 G93A or wild-type SOD1 in primary cultures of astrocytes down-regulates the glutamate transporter GLT-1
14690536	SOD1	SOD1	2.7	possible that mutations of Cu/Zn Cu Zn superoxide dismutase (SOD1), SOD1 responsible for about 20% of familial ALS down-regulates glutamate transporters
14690536	SOD1	hSOD1	2.7	astrocytes to investigate the effect of the FALS-linked mutant hSOD1(G93A) hSOD1 G93A and wild-type SOD1 (hSOD1wt) hSOD1wt on the glutamate uptake
14690536	SOD1	SOD1	2.7	effect of the FALS-linked mutant hSOD1(G93A) hSOD1 G93A and wild-type SOD1 (hSOD1wt) hSOD1wt on the glutamate uptake system
14690536	SOD1	hSOD1	2.7	and RT-PCR it was shown that expression of either hSOD1(G93A) hSOD1 G93A or hSOD1wt in astrocytes produced down-regulation of the levels
14690536	SOD1	hSOD1	2.7	glutamate transporter GLT-1 without alterations in its mRNA level hSOD1(G93A) hSOD1 G93A or hSOD1wt expression caused a decrease of the monomeric
14690536	SOD1	hSOD1	2.7	protein 3H d-aspartate uptake was reduced in cultures expressing hSOD1(G93A) hSOD1 G93A or hSOD1wt
14690536	SOD1	hSOD1	2.7	7'-dichlorofluorescein (DCF)-induced DCF -induced fluorescence revealed that expression of hSOD1(G93A) hSOD1 G93A or hSOD1wt in astrocytes does not lead to detectable
14690536	SOD1	hSOD1	2.7	GLT-1 protein in astrocytes are reduced rapidly by overexpression of hSOD1 and is due to a property shared between the wild-type
14698606	SOD1	SOD1	2.2	linked to mutations in the enzyme superoxide dismutase 1 (SOD1) SOD1
14698606	SOD1	SOD1	2.2	recent years has addressed crucial issues including actions of mutant SOD1 modulation of glutamate transport roles of inflammation and the formation
14698606	SOD1	SOD1	2.2	reported in end-stage ALS 34 as well as in some SOD1 transgenic mice 37
14698606	SOD1	SOD1	2.2	transporter peptides have been reported in both ALS and the SOD1 mutant mouse model 46 and 47
14698606	SOD1	SOD1	2.2	enzyme cyclooxygenase 2 (COX-2) COX-2 have shown beneficial effects in SOD1 mutant mouse models 49 and 50
14698606	SOD	SOD	2.2	Another potential cause of aberrant oxidation is the mutant SOD itself
14698606	SOD1	SOD1	2.2	occurs in an annular pattern immediately surrounding motor neurons in SOD1 mutant mice 54 ( Figure 2c
14698606	SOD1	SOD1	2.2	explain how seemingly disparate inciting factors (for for instance mutant SOD1 environmental toxins trauma inflammation or infection could converge into a
14698606	SOD1	SOD1	2.2	are integrally involved in disease pathogenesis expression of the mutant SOD1 in either motor neurons or astrocytes alone did not cause
14698606	SOD1	SOD1	2.2	Furthermore recent studies of mutant SOD1 chimeras indicate the dependence of motor neuron survival on the
14739060	SOD	SOD	1.3	of motor neurons caused by a missense mutation of CuZn SOD (SOD1) SOD1 is an illustration of how these mechanisms can
14739060	SOD1	SOD1	2.1	neurons caused by a missense mutation of CuZn SOD (SOD1) SOD1 is an illustration of how these mechanisms can lead to
14739060	SOD1	SOD1	2.1	In transgenic mice expressing the human mutant SOD1 gene syndrome develops with many features of ALS including specific
14739060	SOD1	SOD1	2.1	to compare the evolution for motor neurons degeneration in mutant SOD1 transgenic mouse with non-transgenic mouse and normal human SOD1 transgenic
14739060	SOD1	SOD1	2.1	mutant SOD1 transgenic mouse with non-transgenic mouse and normal human SOD1 transgenic mouse 46 50 47 48 and 49
14739060	SOD1	SOD1	2.1	The toxicity of mutant SOD1 seems to be due to a gain of function of
14739060	SOD1	SOD1	2.1	It is also conceivable mutant SOD1 denatures more quickly in vivo than the normal form and
14739060	SOD1	SOD1	2.1	Oxidative stress may be involved in misfolding of mutant SOD1 to form abnormal protein aggregates found as early as 1_amp_#xa0
14739060	SOD1	SOD1	2.1	disorganization of intermediate filaments could be due also to mutant SOD1 induced toxicity as their proteins are vulnerable to oxidative damage
14739060	SOD1	SOD1	2.1	in patients with sporadic ALS and in transgenic mice with SOD1 mutations
14739060	SOD	SOD	1.3	of ubiquinated cytoplasmic inclusion bodies some of which contain aggregated SOD 46
14739060	SOD1	SOD1	2.1	The studies on mutant SOD1 transgenic mice 46 and 63 revealed an up-regulation of gene
15031734	SOD	SOD	2.2	the activity of the antioxidant proteins catalase superoxide dismutase ( SOD glutathione peroxidase and glutathione reductase are increased in the HIPPOCAMPUS
15031734	SOD1	SOD1	1.9	neurodegenerative disorders (A A beta in AD alpha-synuclein in PD SOD1 in ALS frataxin in Friedreich's ataxia ( Box 1 and
15031734	SOD1	SOD1	1.9	with the resulting coordination sphere reminiscent of that observed in SOD1 ( Fig 2
15031734	SOD	SOD	2.2	protein in neural tissue in this instance copper/zinc copper zinc SOD 89
15031734	SOD	SOD	2.2	There are more than 100 mutations of SOD associated with the familial forms of the disease
15031734	SOD	SOD	2.2	these mutations lead to a toxic gain of function by SOD 90
15031734	SOD	SOD	2.2	that the toxicity is due to misfolded aggregated forms of SOD whereas the other proposes that SOD becomes a pro-oxidant protein
15031734	SOD	SOD	2.2	misfolded aggregated forms of SOD whereas the other proposes that SOD becomes a pro-oxidant protein generating ROS
15031734	SOD	SOD	2.2	Mutations of SOD a cupro-enzyme that detoxifies the ROS superoxide can convert the
15031734	SOD	SOD	2.2	These initial observations suggested that the toxicity associated with mutant SOD is the result of a corruption of the active site
15031734	SOD	SOD	2.2	However if the copper at the active site of SOD is the culprit behind the toxicity then knocking out the
15031734	SOD	SOD	2.2	is the culprit behind the toxicity then knocking out the SOD copper chaperone (CCS), CCS which loads copper into the active
15031734	SOD	SOD	2.2	this hypothesis Subramaniam 97 crossed CCS knockout mice with an SOD mutant ALS mouse model the phenotype of this cross showed
15031734	SOD	SOD	2.2	ALS mouse model the phenotype of this cross showed reduced SOD activity which is consistent with a low copper load in
15031734	SOD	SOD	2.2	the possibility that other redox-active lower-affinity metal-binding sites exist on SOD
15031734	SOD	SOD	2.2	98 and in vitro studies 99 with an H46R mutant SOD linked to familial ALS and which has no SOD activity
15031734	SOD	SOD	2.2	mutant SOD linked to familial ALS and which has no SOD activity have shown that a surface-exposed cysteine residue in SOD
15031734	SOD	SOD	2.2	SOD activity have shown that a surface-exposed cysteine residue in SOD is also capable of coordinating copper and is redox active
15031734	SOD	SOD	2.2	glucose transporter type-3 glutathione peroxidase glutathione reductase mitogen-activated protein kinase-1 SOD alpha-synuclein xanthine dehydrogenase
15031734	SOD	SOD	2.2	A beta amyloid-beta ROS reactive oxygen species SOD superoxide dismutase
15031734	SOD	SOD	2.2	The normal function of superoxide dismutase (SOD) SOD is to convert toxic superoxide radicals into H 2 O
15031734	SOD	SOD	2.2	With age-dependent increases in copper levels low-affinity copper sites on SOD such as Cys111 are occupied these sites are redox active
15208263	SOD1	SOD1	1.2	for the ubiquitous anti-oxidant enzyme Cu Zn superoxide dismutase (SOD1) SOD1 are associated with familial amyotrophic lateral sclerosis (fALS), fALS a
15208263	SOD1	SOD1	1.2	Expression of a mutant SOD1 typical of fALS patients restricted to either motor neurons or
15208263	SOD1	SOD1-linked	1.2	This cross-talk may be crucial for the pathogenesis of SOD1-linked fALS but also for the more common sporadic form of
15289674	SOD1	SOD1	2.7	Mutations in Cu/Zn-superoxide Cu Zn-superoxide dismutase (SOD1) SOD1 gene have been identified in familial amyotrophic lateral sclerosis
15289674	SOD1	SOD1	2.7	hybrid cells (VSC4.1) VSC4.1 constitutively expressing a mutant (G93A) G93A SOD1
15333927	SOD	SOD	1.4	Cu Zn superoxide dismutase (Cu,Zn Cu Zn SOD is an essential enzyme for protecting cells from the toxic
15333927	SOD	SOD	1.4	In humans two distinct Cu Zn SOD genes are located on chromosomes 4 and 21 and mutations
15333927	SOD	SODs	0.9	chronically debilitating disease schistosomiasis also produce two distinct Cu Zn SODs in this case one cytosolic and one bearing a signal
15812313	SOD1	SOD1	3.2	Mutations in the copper_amp_#47 zinc superoxide dismutase (SOD1) SOD1 gene are known to be responsible for familial amyotrophic lateral
15812313	SOD1	SOD1	3.2	Alteration of metal binding properties of mutant SOD1 has been proposed to play a role in the pathogenesis
15812313	SOD1	SOD1	3.2	excess extracellular copper on motor neuronal cells expressing human mutant SOD1 (G93A), G93A and evaluated the neuroprotective effects of energy metabolism
15812313	SOD1	SOD1	3.2	Motoneuron-neuroblastoma hybrid (VSC VSC 4.1 cells expressing mutant SOD1 when treated with copper chloride showed reduced viability and increased
15812313	SOD1	SOD1	3.2	and production of reactive oxygen species in cells expressing mutant SOD1
15812313	SOD1	SOD1	3.2	The mutation in the copper_amp_#47 zinc superoxide dismutase (SOD1) SOD1 gene is known to be associated with the familial ALS
15812313	SOD1	SOD1	3.2	ALS (FALS) FALS because of some undefined property of mutant SOD1 protein _amp_#91 1 _amp_#93
15812313	SOD1	SOD1	3.2	SOD1 mutations cause the disease through a gain of function or
15812313	SOD	SOD	2.2	of function or by enhancing an unknown nondismutase activity of SOD _amp_#91 2 _amp_#93
15812313	SOD1	SOD1	3.2	Several pathophysiological mechanisms linking the SOD1 mutation with FALS have been proposed
15812313	SOD1	SOD1	3.2	They include a failure to fold or degrade mutant SOD1 the formation of free radicals the susceptibility of mutant SOD1
15812313	SOD1	SOD1	3.2	SOD1 the formation of free radicals the susceptibility of mutant SOD1 to disulfide reduction and the release of free copper _amp_#91
15812313	SOD1	SOD1	3.2	hypotheses have been proposed concerning the metal binding properties of SOD1
15812313	SOD1	SOD1	3.2	(NO), NO reacts with the Cu 2_amp_#43 ion of mutant SOD1 to produce nitronium ions which then nitrate proteins and induce
15812313	SOD1	SOD1	3.2	and Yim et al _amp_#91 7 _amp_#93 reported that mutant SOD1 has higher peroxidase activity than the wild type (WT), WT
15812313	SOD1	SOD1	3.2	et al _amp_#91 8 _amp_#93 proposed that the FALS-associated mutant SOD1 failed to bind or shield Cu 2_amp_#43 as effectively as
15812313	SOD1	SOD1	3.2	by a mechanism involving the altered copper-dependent activity of mutant SOD1
15812313	SOD1	SOD1	3.2	If an altered copper binding capacity by SOD1 protein causes a toxic gain of function neurons with SOD1
15812313	SOD1	SOD1	3.2	SOD1 protein causes a toxic gain of function neurons with SOD1 mutations are likely to be more vulnerable to excess copper
15812313	SOD1	SOD1	3.2	Furthermore mutant SOD1 mice have significant elevations in brain or spinal cord copper
15812313	SOD1	SOD1	3.2	elevation of copper is probably copper bound to the over-expressed SOD1
15812313	SOD1	SOD1	3.2	Therefore SOD1 mutant neurons would be more vulnerable to an exogenous load
15812313	SOD1	SOD1	3.2	WT or mutant (G93A) G93A human SOD1 cDNA (a a gift from Dr Lawrence J Hayward University
15812313	SOD1	SOD1	3.2	USA with pcDNA3.1 vector containing cDNA encoding WT or G93A SOD1 and then selected using geneticin (G418 G418 sulfate Gibco
15812313	SOD1	SOD1	3.2	or pooled colonies were used for experiments after determining human SOD1 expression by Western blot and immunohistochemical staining
15812313	SOD1	SOD1	3.2	The cells expressing human SOD1 were cultured in a medium containing geneticin at 200 microg_amp_#47
15812313	SOD1	SOD1	3.2	(Cu Cu 2_amp_#43 on the death of cells expressing mutant SOD1 the cells were treated with various agents prior to exposing
15812313	SOD1	SOD1	3.2	VSC 4.1 cells expressing human WT or mutant SOD1 (G93A) G93A were exposed to increasing concentrations of Cu 2_amp_#43
15812313	SOD1	SOD1	3.2	treatment (250 250 microM in cells expressing WT or mutant SOD1
15812313	SOD1	SOD1	3.2	In cells expressing WT SOD1 Cu 2_amp_#43 -induced cell death was not affected by trolox
15812313	SOD1	SOD1	3.2	attenuate Cu 2_amp_#43 -induced neuronal death in cells expressing mutant SOD1 ( Fig 2a
15812313	SOD1	SOD1	3.2	concentrations reduce the survival of VSC 4.1 cells expressing human SOD1 mutated at G93A and that pyruvate protects these cells from
15812313	SOD1	SOD1	3.2	functioning of several enzymes including cytochrome c oxidase ceruloplasmin and SOD1 _amp_#91 13 _amp_#93
15812313	SOD1	SOD1	3.2	2_amp_#43 reduces the viability of VSC 4.1 cells expressing mutant SOD1 (G93A) G93A
15812313	SOD1	SOD1	3.2	through this property in VSC 4.1 cells harboring the G93A SOD1 mutation
15812313	SOD1	SOD1	3.2	free radical scavenging action in VSC 4.1 cells expressing mutant SOD1 (G93A) G93A
15812313	SOD1	SOD1	3.2	found to be toxic to motor neuronal cells expressing mutant SOD1 and pyruvate attenuated this Cu 2_amp_#43 -induced neuronal death
15812313	SOD1	SOD1	3.2	and energy metabolism enhancing actions in motor neurons harboring the SOD1 mutation
15850589	SOD1	SOD1	5.7	Mutations of Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 are found in patients with familial amyotrophic lateral sclerosis (FALS)
15850589	SOD1	SOD1	5.7	with human wild type (wt) wt or mutant (G93A) G93A SOD1
15850589	SOD1	SOD1	5.7	In conclusion even a small amount of mutant SOD1 put motor neurons in a condition of oxidative stress and
15850589	SOD1	SOD1	5.7	the gene encoding for Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 and over 100 missense mutations have been described
15850589	SOD1	SOD1	5.7	SOD1 is a free radical-scavenging enzyme since it converts the superoxide
15850589	SOD1	SOD1	5.7	is now generally accepted that the toxic effect of mutant SOD1 is not due to the loss of dismutase activity but
15850589	SOD1	SOD1	5.7	oxidative chemistry and/or and or misfolding and aggregation of mutant SOD1 (for for a review see Ref 1
15850589	SOD1	SOD1	5.7	Apparently mutation converts SOD1 from an anti-apoptotic gene to a pro-apoptotic one 2 3
15850589	SOD1	SOD1	5.7	The presence of SOD1 not only in the cytosol but also in the mitochondrial
15850589	SOD1	SOD1	5.7	and in vitro models were generated by genetic manipulation of SOD1 expression
15850589	SOD1	SOD1	5.7	previous in vitro studies of the toxic effects of mutant SOD1 were conducted in cells which did not have a motor
15850589	SOD1	SOD1	5.7	However while mutant SOD1 is ubiquitously expressed the selectivity of damage towards motor neurons
15850589	SOD1	SOD1	5.7	that this cell type has a peculiar susceptibility to mutant SOD1 toxicity
15850589	SOD1	SOD1	5.7	Accordingly microinjected mutant SOD1 protein caused death in primary motor neurons but not in
15850589	SOD1	SOD1	5.7	review see Ref 10 and by a selective enrichment of SOD1 in motor neurons of the spinal cord and brainstem 11
15850589	SOD1	SOD1	5.7	Recently the effects of human mutant SOD1 were investigated in the NSC-34 motor neuron-like cell line 12
15850589	SOD1	SOD1	5.7	wt or mutant G93ASOD1 and investigated the toxicity of mutant SOD1 expressed at levels close to those seen in the human
15850589	SOD1	SOD1	5.7	and generation of NSC-34 cell lines stably transfected with human SOD1
15850589	SOD1	SOD1	5.7	with the vector cloned with wt or G93A mutant human SOD1 cDNAs 16 using the LipofectAMINE PLUS reagent (Invitrogen Invitrogen Life
15850589	SOD1	SOD1	5.7	clones were isolated grown and tested for expression of human SOD1 protein by Western blotting
15850589	SOD1	SOD1	5.7	The NSC-34 cell lines transfected with vv or wt SOD1 or G93ASOD1 were maintained in selective medium (0.5 0.5 mg/mL
15850589	SOD1	SOD1	5.7	SDS PAGE and Western blotting of SOD1
15850589	SOD1	SOD1	5.7	Protein bands identified by SOD1 antibody were detected using the ECL-Plus detection system (Amersham Amersham
15850589	SOD1	SOD1	5.7	The continued expression of wt and G93A human SOD1 was routinely checked in order to ensure the cell lines
15850589	SOD1	SOD1	5.7	cell lines expressed similar quantities of human wt and mutant SOD1
15850589	SOD1	SOD1s	2.4	The expression of human SOD1s was measured with an anti-human SOD1 antibody which also cross-reacts
15850589	SOD1	SOD1	5.7	The expression of human SOD1s was measured with an anti-human SOD1 antibody which also cross-reacts with murine SOD1
15850589	SOD1	SOD1	5.7	with an anti-human SOD1 antibody which also cross-reacts with murine SOD1
15850589	SOD1	SOD1s	2.4	In SDS-PAGE human SOD1s migrate at a slower rate than mouse SOD1 18 and
15850589	SOD1	SOD1	5.7	SDS-PAGE human SOD1s migrate at a slower rate than mouse SOD1 18 and accordingly two bands were detected with mouse SOD1
15850589	SOD1	SOD1	5.7	SOD1 18 and accordingly two bands were detected with mouse SOD1 being the band with the lower molecular weight
15850589	SOD1	SOD1	5.7	No human SOD1 expression is seen in cells transfected with empty vector
15850589	SOD1	SOD1	5.7	in this study was about 30% of the endogenous mouse SOD1 as measured by densitometry ( Fig 1 C
15850589	SOD1	SOD1	5.7	observed in NSC-34 cells transfected with the wt form of SOD1 while a shift towards a higher DCF fluorescence level was
15850589	SOD1	SOD1	5.7	level was observed in NSC-34 cells transfected with the mutant SOD1 protein ( Fig 3 A
15850589	SOD1	SOD1	5.7	quantified measuring the average DCF fluorescence of living untransfected wt SOD1 and G93ASOD1 transfected cells ( Fig 3 B
15850589	SOD1	SOD1	5.7	This suggests the two forms of SOD1 handle free radicals differently
15850589	SOD1	SOD1	5.7	of cells with depolarized mitochondria compared to untransfected or wt SOD1 transfected cell lines ( Fig 4 A
15850589	SOD1	SOD1	5.7	3 days limited the MTT reduction in NSC-34 expressing mutant SOD1 protein more than in NSC-34 expressing wt SOD1 or untransfected
15850589	SOD1	SOD1	5.7	expressing mutant SOD1 protein more than in NSC-34 expressing wt SOD1 or untransfected cells ( Fig 5 A
15850589	SOD1	SOD1	5.7	h caused preferential toxicity towards cells transfected with the mutant SOD1 (about about 35% decrease Fig 5 C
15850589	SOD1	SOD1	5.7	(NSC-34) NSC-34 stably expressing the human mutant G93A form of SOD1 as representative of the SOD1 mutant forms seen in about
15850589	SOD1	SOD1	5.7	human mutant G93A form of SOD1 as representative of the SOD1 mutant forms seen in about 20% of FALS patients
15850589	SOD1	SOD1	5.7	containing G93ASOD1 had a lower viability than those expressing wt SOD1
15850589	SOD1	SOD1	5.7	though it was expressed at a lower level than normal SOD1 a condition similar to FALS
15850589	SOD1	SOD1s	2.4	Apoptotic cell death by mutant SOD1s was shown in other cellular models but in these studies
15850589	SOD1	SOD1	5.7	was not investigated whether the expression level of the mutant SOD1 proteins was comparable to the level observed in the FALS
15850589	SOD1	SOD1	5.7	The effect of mutant SOD1 on viability appeared when motor neurons were in the growth
15850589	SOD1	SOD1	5.7	event is the enhanced ROS formation in cells containing mutant SOD1
15850589	SOD1	SOD1	5.7	This effect is peculiar to G93ASOD1 and wt SOD1 might in fact afford protection since it lowered intracellular ROS
15850589	SOD1	SOD1	5.7	was also reduced in human neuroblastoma SH-SY5Y cells expressing mutant SOD1 in a ratio of 1 1 with the endogenous SOD1
15850589	SOD1	SOD1	5.7	SOD1 in a ratio of 1 1 with the endogenous SOD1 protein 24 and in primary motor neurons from G93A mice
15850589	SOD1	SOD1	5.7	The presence of mutant SOD1 in our cellular model caused the appearance of a population
15850589	SOD1	SOD1	5.7	Mitochondria of mutant SOD1 transgenic mice are also swollen and in addition abnormally vacuolated
15850589	SOD1	SOD1	5.7	damage with some relationship with the high content of mutant SOD1 in some of these in vivo experimental models
15850589	SOD1	SOD1	5.7	more affected in these cells than in NSC-34 expressing wt SOD1 after exposure to rotenone EA or serum withdrawal
15850589	SOD1	SOD1	5.7	Altered ETC activities were shown in FALS patients with SOD1 mutations (for for a review see Ref 9 in mutant
15850589	SOD1	SOD1	5.7	mutations (for for a review see Ref 9 in mutant SOD1 transgenic mice 31 and 32 and in a cell culture
15850589	SOD1	SOD1	5.7	motor neurons to excitotoxicity 36 and motor neurons containing mutant SOD1 were more vulnerable to glutamate 25
15850589	SOD1	SOD1	5.7	A fraction of SOD1 is located in this space with the putative function to
15850589	SOD1	SOD1	5.7	The presence of mutant SOD1 in the intermembrane space of FALS mitochondria might however be
15850589	SOD1	SOD1-associated	2.4	mitochondria might however be critical in the pathogenesis of mutant SOD1-associated FALS 32 38 and 39
15850589	SOD1	SOD1	5.7	Our study shows that overexpression of wt SOD1 did indeed reduce the ROS level in viable motor neurons
15850589	SOD1	SOD1	5.7	disease onset and prolonged survival in transgenic mice with mutant SOD1 42 43 and 44 and rendered cells transfected with mutant
15850589	SOD1	SOD1	5.7	42 43 and 44 and rendered cells transfected with mutant SOD1 more resistant to apoptosis 45
15850589	SOD1	SOD1	5.7	scavengers reversed mitochondrial dysfunction and cell death due to mutant SOD1 in cell culture models of FALS 12 and 35 and
15850589	SOD1	SOD1	5.7	In conclusion this study found that motor neurons containing mutant SOD1 in amounts comparable to FALS patients are in a condition
15850589	SOD1	SOD1	5.7	determining the cell destiny in the presence of the mutant SOD1
15850589	SOD1	SOD1	5.7	Fig 1._amp_#xa0 Morphology and transfection of NSC-34 cells with human SOD1
15850589	SOD1	SOD1	5.7	Panels B and C show the expression of human SOD1 after transient or stable transfection of NSC-34 cells with empty
15850589	SOD1	SOD1	5.7	cells with empty vector wild type or G93A mutant human SOD1
15850589	SOD1	SOD1	5.7	upper and lower bands correspond to the human and murine SOD1 respectively
15850589	SOD1	SOD1	5.7	Fig 6._amp_#xa0 Effect of sodium butyrate on expression of human SOD1 and mitochondrial function
15850589	SOD1	SOD1	5.7	shows the Western blot analysis of human wt or G93A SOD1 expression after 24 h treatment with sodium butyrate (NaB; NaB
15863242	SOD1	SOD1	2.5	Cu/Zn-superoxide Cu Zn-superoxide dismutase 1 (SOD1), SOD1 encoded on chromosome 21 is a key enzyme in metabolism
15863242	SOD1	SOD1	2.5	Transgenic mice overexpressing human SOD1 (Tg-hSOD1) Tg-hSOD1 are useful model for Down syndrome (trisomy trisomy
15863242	SOD1	SOD1	2.5	Our findings suggest that overexpressed SOD1 directly or by generating reactive oxygen species may lead to
15863242	SOD1	hSOD1	3.0	The human Cu/Zn-superoxide Cu Zn-superoxide dismutase 1 gene (hSOD1) hSOD1 was the first chromosome 21 gene to be characterised (
15863242	SOD1	SOD1	2.5	Later studies revealed overexpression of SOD1 mRNA protein and increased activity was detected in brains of
15863242	SOD1	SOD1	2.5	Moreover transgenic mice expressing wild-type human SOD1 (Tg-hSOD1 Tg-hSOD1 mice were the first model for DS (
15863242	SOD1	SOD1	2.5	deficit in DS no proof for a pathogenetic role of SOD1 in DS exists
15863242	SOD1	SOD1	2.5	Although increased SOD1 may lead to generation of reactive oxygen species and thus
15863242	SOD1	SOD1	2.5	role in neurodegenerative mechanisms it was demonstrated that overexpression of SOD1 may be protective against apoptosis for hippocampal neurons ( Korenberg
15863242	SOD1	hSOD1	3.0	Transgenic mice about 3-month-old male harbouring the hSOD1 gene were obtained from Dr Jacqueline London University of Paris
15863242	SOD1	hSOD1	3.0	Generation of the hSOD1 transgenic line KT has been described previously ( Paris et
15863242	SOD1	hSOD1	3.0	by injecting an 11.5 kb EcoRI_amp_#x2013 BamH1 fragment containing the hSOD1 gene into fertilised eggs from FVB/N FVB N mice
15863242	SOD1	SOD1	2.5	Measurement of SOD1 activity and immunostaining in WT and Tg-hSOD1
15863242	SOD1	hSOD1	3.0	For hSOD1 activity measurements hippocampal extracts of WT and Tg-hSOD1 mice were
15863242	SOD1	SOD1	2.5	Activity of SOD1 was assayed photochemically by measuring inhibition of nitroblue tetrazolium reduction
15863242	SOD1	hSOD1	3.0	In Tg-hSOD1 mice immunostaining for hSOD1 was strong in the brain and no immunostaining occurred in
15863242	SOD1	hSOD1	3.0	the CNS of WT indicating that labeling was specific for hSOD1 ( Jaarsma et al. 2000
15863242	SOD1	SOD1	2.5	Increased activity of SOD1 in hippocampus of Tg-hSOD1
15863242	SOD1	SOD1	2.5	Overexpression of SOD1 in hippocampus was evaluated by enzymatic activity using the classic
15863242	SOD1	SOD1	2.5	the classic test of inhibition of nitroblue tetrazolium reduction by SOD1 and automatically assayed using a Ransod kit
15863242	SOD1	SOD1	2.5	The SOD1 activity was increased by factor 5 in blood
15863242	SOD1	SOD1	2.5	in hippocampus of 3-month-old Tg-SOD1 showed large increases in total SOD1 activity WT (2.5 2.5 _amp_#xb1 0.17 U/mg), U mg hemizygotes
15863242	SOD1	hSOD1	3.0	WT (2.5 2.5 _amp_#xb1 0.17 U/mg), U mg hemizygotes (hSOD1/+, hSOD1 38.87 _amp_#xb1 2.04 U/mg) U mg and homozygotes (hSOD1/hSOD1, hSOD1
15863242	SOD1	hSOD1	3.0	hSOD1 38.87 _amp_#xb1 2.04 U/mg) U mg and homozygotes (hSOD1/hSOD1, hSOD1 hSOD1 47.79 _amp_#xb1 1.69 U/mg) U mg
15863242	SOD1	hSOD1	3.0	38.87 _amp_#xb1 2.04 U/mg) U mg and homozygotes (hSOD1/hSOD1, hSOD1 hSOD1 47.79 _amp_#xb1 1.69 U/mg) U mg
15863242	SOD1	hSOD1	3.0	large series of proteins were successfully represented and even transgenic hSOD1 was detected in 2-DE gels of Tg-hSOD1 mice ( Fig
15863242	SOD1	SOD1	2.5	Antioxidant proteins showed no different expression except mouse SOD1 (mSOD1) mSOD1 (Unpublished Unpublished data Shin et al. 2003
15863242	SOD1	mSOD1	1.7	Antioxidant proteins showed no different expression except mouse SOD1 (mSOD1) mSOD1 (Unpublished Unpublished data Shin et al. 2003
15863242	SOD1	mSOD1	1.7	In addition spots of mSOD1 and hSOD1 showing high similarity ( Fig 3 (A)) A
15863242	SOD1	hSOD1	3.0	In addition spots of mSOD1 and hSOD1 showing high similarity ( Fig 3 (A)) A were detected
15863242	SOD1	hSOD1	3.0	We observed that expression level of hSOD1 in hippocampus of homozygotes was significantly higher than that in
15863242	SOD1	mSOD1	1.7	_amp_#xb1 1.804 versus 12.244 _amp_#xb1 2.259 P = 0.0259 while mSOD1 was significantly decreased in hippocampus of Tg-hSOD1 mice (Unpublished Unpublished
15863242	SOD1	SOD1-dependent	1.7	in hemizygous or homozygous Tg-hSOD1 mice revealing directly or indirectly SOD1-dependent alterations of several protein pathways and cascades systems that are
15863242	SOD1	SOD1	2.5	the gamma subunit was here observed in hippocampus in the SOD1 overexpression animal model of DS
15863242	SOD1	SOD1-mediated	2.0	catalyzing covalent attachment of ubiquitin to other proteins may reflect SOD1-mediated impaired protein handling in terms of ubiquitination
15863242	SOD1	SOD1	2.5	Multiple protein derangement may directly or indirectly depend on SOD1 overexpression impairment of translation (translation translation elongation or simply reflect
15863242	SOD1	mSOD1	1.7	Spots of mSOD1 and hSOD1 were demonstrated in hippocampus of Tg-hSOD1 mice
15863242	SOD1	hSOD1	3.0	Spots of mSOD1 and hSOD1 were demonstrated in hippocampus of Tg-hSOD1 mice
15863242	SOD1	hSOD1	3.0	Fig 3._amp_#xa0 Comparison of hSOD1 with mSOD1
15863242	SOD1	mSOD1	1.7	Fig 3._amp_#xa0 Comparison of hSOD1 with mSOD1
15863242	SOD1	hSOD1	3.0	(A) A Alignment of hSOD1 (P00441) P00441 with mSOD1 ( P08228
15863242	SOD1	mSOD1	1.7	(A) A Alignment of hSOD1 (P00441) P00441 with mSOD1 ( P08228
15863242	SOD1	hSOD1	3.0	This sequence alignment with CLUSTALW showed that hSOD1 has high similarity to mSOD1
15863242	SOD1	mSOD1	1.7	alignment with CLUSTALW showed that hSOD1 has high similarity to mSOD1
15863242	SOD1	mSOD1	1.7	MALDI-TOF spectrum of mSOD1 (B) B and hSOD1 (C) C
15863242	SOD1	hSOD1	3.0	MALDI-TOF spectrum of mSOD1 (B) B and hSOD1 (C) C
15896810	SOD	SOD	1.4	three times faster than the rate of superoxide dismutase (SOD) SOD in catalyzing the dismutation of the superoxide anion to hydrogen
15896810	SOD	SOD	1.4	Therefore when present at appropriate concentrations NO effectively competes with SOD for O 2 _amp_#x2212
15964487	SOD1	SOD1	1.4	its administration in mice expressing a mutant superoxide dismutase (SOD1(G37R)) SOD1 G37R at late presymptomatic stage delayed the onset of motor
15964487	SOD1	SOD1	1.4	and muscle strength decline and increased the longevity of SOD1(G37R) SOD1 G37R mice ( Kriz et al. 2002
16026864	SOD1	SOD1	2.2	induced by mutations in the enzyme superoxide dismutase 1 (SOD1) SOD1
16026864	SOD1	SOD1	2.2	For the well-studied familial form of ALS induced by mutant SOD1 the involvement of Ca 2 has been demonstrated in cell
16026864	SOD1	SOD1	2.2	given by the inhibition of glial glutamate transport by mutant SOD1 and the consecutive disturbance of Ca 2 homeostasis by excitotoxic
16026864	SOD1	SOD1-related	2.2	the importance of Ca 2 -permeable AMPA receptors in mutant SOD1-related ALS
16026864	SOD1	SOD1	2.2	Ca 2 -permeable AMPA receptors and survival times of transgenic SOD1 mice were significantly increased following chronic treatment with AMPA receptor
16026864	SOD1	SOD1	2.2	addition to glutamate receptors in mediating the toxicity of mutant SOD1 in motoneurons
16026864	SOD1	SOD1	2.2	-permeable AMPA receptors was further underlined by cross-breeding of transgenic SOD1 mice with mice that showed markedly reduced Ca 2 permeability
16026864	SOD1	SOD1	2.2	Aggregates containing mutant SOD1 have been found within the mitochondrial matrix 42 43 and
16026864	SOD1	SOD1	2.2	Most interestingly recent work provided evidence that mutant SOD1 might disrupt association of complex IV (cytochrome cytochrome c with
16026864	SOD1	SOD1	2.2	This has been demonstrated for cultured motoneurons expressing mutant SOD1 49 and is in line with a study of motoneurons
16026864	SOD1	SOD1	2.2	Cross-breeding these mice with the SOD1 mutants severely enhanced motoneuron degeneration 55 whereas treatment of SOD-transgenic
16026864	SOD	SOD-transgenic	2.2	SOD1 mutants severely enhanced motoneuron degeneration 55 whereas treatment of SOD-transgenic mice with VEGF delayed progression of symptoms and prolonged survival
16026864	SOD1	SOD1	2.2	Briefly mitochondrial respiration can be disturbed by mutations in SOD1 hypoxia Ca 2 overload or alterations in the mitochondrial genome
16026864	SOD1	SOD1	2.2	disturbance of mitochondrial respiration by mutant superoxide dismutase 1 (SOD1) SOD1 or hypoxia results in increased formation of reactive oxygen species
16043017	SOD1	SOD1	2.7	caused by a gain-of-function mutation in Cu Zn-superoxide dismutase (SOD1) SOD1
16043017	SOD	SOD	1.9	proposed to explain the toxic gain of function of mutant SOD (mSOD) mSOD
16043017	SOD	mSOD	1.9	explain the toxic gain of function of mutant SOD (mSOD) mSOD
16043017	SOD	mSOD	1.9	One is that mSOD can directly promote reactive oxygen species and reactive nitrogen species
16043017	SOD1	SOD1	2.7	These proteins are SOD1 translationally controlled tumor protein (TCTP), TCTP ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1),
16043017	SOD1	SOD1	2.7	our current study suggests that oxidative modification of UCH-L1 TCTP SOD1 and possibly B-crystallin may play an important role in the
16043017	SOD1	SOD1	2.7	caused by a gain-of-function mutation in Cu Zn-superoxide dismutase (SOD1) SOD1 3 and 4
16043017	SOD1	SOD1	2.7	SOD1 catalyzes the disproportionation of superoxide anion radical to hydrogen peroxide
16043017	SOD1	SOD1	2.7	Over 100 different missense substitutions in the 153-amino-acid SOD1 have been described in individuals and kindreds affected by SOD1-linked
16043017	SOD1	SOD1-linked	1.9	SOD1 have been described in individuals and kindreds affected by SOD1-linked FALS 5
16043017	SOD1	SOD1	2.7	One of the most common mutations of SOD1 is the substitution of glycine by alanine at residue 93
16043017	SOD	SOD	1.9	proposed to explain the toxic gain of function of mutant SOD (mSOD) mSOD 6
16043017	SOD	mSOD	1.9	explain the toxic gain of function of mutant SOD (mSOD) mSOD 6
16043017	SOD	mSOD	1.9	One is that mSOD can directly promote reactive oxygen species and reactive nitrogen species
16043017	SOD	mSOD	1.9	in tissues from ALS patients 23 24 and 25 and mSOD transgenic mice 22 and 26 reportedly are rich in mSOD
16043017	SOD	mSOD	1.9	mSOD transgenic mice 22 and 26 reportedly are rich in mSOD ubiquitin and neurofilament proteins
16043017	SOD1	SOD1-related	1.9	oxidative modification of macromolecules was demonstrated in neuronal tissues of SOD1-related FALS patients and transgenic mice 30 31 and 32
16043017	SOD1	mSOD1	1.9	Enhanced susceptibility of exogenous oxidative stress in mSOD1 cell cultures was also observed in in vitro studies 33
16043017	SOD	mSOD	1.9	Exogenous oxidative stress can even inhibit the rapid degradation of mSOD 36
16043017	SOD1	SOD1	2.7	higher capacity to generate free radicals 9 compared to wild-type SOD1
16043017	SOD1	SOD1	2.7	of the oxidatively modified proteins in G93A-SOD1 transgenic mice is SOD1 32 indicating that oxidation of SOD1 is likely important to
16043017	SOD1	SOD1	2.7	G93A-SOD1 transgenic mice is SOD1 32 indicating that oxidation of SOD1 is likely important to the development of this model of
16043017	SOD1	SOD1	2.7	Transgenic mice expressing the human SOD1 gene with a G93A mutation strain B6SJL/TgN B6SJL TgN (SOD1-G93A)-2Gur)
16043017	SOD1	SOD1	2.7	These proteins were identified as SOD1 translationally controlled tumor protein (TCTP), TCTP UCH-L1 and B-crystallin
16043017	SOD1	SOD1	2.7	We report here that the specific carbonyl levels of human SOD1 TCTP UCH-L1 and possibly B-crystallin are significantly increased in the
16043017	SOD1	SOD1	2.7	Spots close to human SOD1 are modified SOD1 possibly phosphorylated SOD1
16043017	SOD1	SOD1	2.7	Spots close to human SOD1 are modified SOD1 possibly phosphorylated SOD1
16043017	SOD1	SOD1	2.7	Spots close to human SOD1 are modified SOD1 possibly phosphorylated SOD1
16043017	SOD	SOD	1.9	provide insight into the mechanisms of the neurotoxicity of mutant SOD in vivo
16043017	SOD1	SOD1	2.7	It is well established that mutant SOD1 enhances oxidative activity by acting as a peroxidase 9 11
16043017	SOD1	SOD1	2.7	carbonyl levels compared to those of the nontransgenic mice as SOD1 TCTP UCH-L1 and B-crystallin
16043017	SOD1	SOD1	2.7	SOD1 previously was identified immunochemically as one of the oxidatively modified
16043017	SOD1	SOD1	2.7	proteomics approach to confirm that the specific carbonyl level of SOD1 is increased in the spinal cords of G93A-SOD1 transgenic mice
16043017	SOD1	SOD1	2.7	Although G93A-SOD1 shows dismutation activity identical to that of wild-type SOD1 the activity of SOD1 in FALS patients with mutations is
16043017	SOD1	SOD1	2.7	activity identical to that of wild-type SOD1 the activity of SOD1 in FALS patients with mutations is decreased 50% in motor
16043017	SOD1	SOD1	2.7	radical production in the G93A-SOD1 transgenic animals is induced by SOD1 mutation 32 alteration of tumor necrosis factor TNF- and TNF--modulating
16043017	SOD1	SOD1	2.7	study is consistent with the notion that oxidative modification of SOD1 plays a role in the neurotoxicity of mutant SOD1 in
16043017	SOD1	SOD1	2.7	of SOD1 plays a role in the neurotoxicity of mutant SOD1 in the disease
16043017	SOD1	mSOD1	1.9	G93A-SOD1 mouse spinal cord the inclusions of human ALS and mSOD1 (including including G93A mice are excessively ubiquitinated 79 80 81
16043017	SOD1	SOD1	2.7	Aberrant accumulation of mutant SOD1 is demonstrated in Caenorhabditis elegans expressing human mutant SOD1 36
16043017	SOD1	SOD1	2.7	mutant SOD1 is demonstrated in Caenorhabditis elegans expressing human mutant SOD1 36
16043017	SOD1	SOD1	2.7	Based on our current observations the increased oxidative modification of SOD1 UCH-L1 and B-crystallin plays a significant role in the protein
16043017	SOD1	SOD1	2.7	protein (TCTP) TCTP and proteins involved in inclusion formation (SOD1, SOD1 UCH-L1 and B-crystallin suggesting a potential relationship between protein oxidation
16043017	SOD1	SOD1	2.7	(TCTP), TCTP protein degradation (UCH-L1), UCH-L1 and antioxidant capacity (SOD1) SOD1
16046141	SOD1	SOD1	2.2	the expression of several mutant Cu Zn superoxide dismutases (SOD1) SOD1 typical of familial ALS is mediated by Apaf1 a scaffold
16046141	SOD1	SOD1s	1.7	of neuronal origin and modulating the expression of both mutant SOD1s and Apaf1 we show that the removal of Apaf1 prevents
16046141	SOD1	SOD1	2.2	gene coding for the enzyme Cu Zn superoxide dismutase (SOD1) SOD1 ( Rosen et al. 1993 fALS-SOD1 mutations cause the appearance
16046141	SOD1	SOD1	2.2	paradigms (post-mortem post-mortem samples from patients mice transgenic for mutant SOD1 and cell cultures
16046141	SOD1	SOD1-mediated	1.7	often yielded conflicting results converging evidence indicates that the mutant SOD1-mediated cell death observed in ALS is apoptotic in nature (reviewed
16046141	SOD1	SOD1	2.2	significantly extend the lifespan of transgenic mice overexpressing a fALS-linked SOD1 mutant ( Li et al. 2000
16046141	SOD1	SOD1	2.2	role in the initiation of motor neuron death by mutant SOD1
16046141	SOD1	SOD1	2.2	to be crucial targets of the toxic function of mutant SOD1 ( Mattiazzi et al. 2002 Liu et al. 2004 Pasinelli
16046141	SOD1	SOD1	2.2	coding for wt or G93A G37R G85R and I113T mutant SOD1 were described elsewhere ( Carr_amp_#xec et al. 1997
16046141	SOD1	SOD1	2.2	lines transfected for the transient expression of human wild type SOD1 (named named wt or mutant fALS-SOD1 G93A G37R G85R and
16046141	SOD1	SOD1	2.2	Immunoreactive SOD1 was detected with a rabbit polyclonal antibody (Stratagene) Stratagene
16046141	SOD1	SOD1	2.2	Measurement of SOD1 activity
16046141	SOD1	SOD1	2.2	SOD1 activity was detected as the achromatic band on the violet-colored
16046141	SOD1	SOD1	2.2	1 A under this condition the total level of immunoreactive SOD1 is highly increased with respect to the parental line and
16046141	SOD1	SOD1	2.2	line and 1 day after transfection all lines expressing mutant SOD1 show a remarkable decrease in mitochondrial metabolic activity as indicated
16046141	SOD1	SOD1s	1.7	Materials and methods 48 h after transfection expression of mutant SOD1s induces activation of caspase-3 caspase-9 but not caspase-1 ( Fig
16046141	SOD1	SOD1	2.2	Cell death induced by mutant SOD1 is prevented by treatment both with pan-caspase inhibitor z-VAD and
16046141	SOD1	SOD1-induced	1.7	To analyze whether Apaf1 is involved in mutant SOD1-induced apoptosis we stably transfected SH-SY5Y neuroblastoma cells with a plasmid
16046141	SOD1	SOD1	2.2	is observed in SH/Apaf1 SH Apaf1 cells expressing the mutant SOD1 with respect to untransfected control SH cells
16046141	SOD1	SOD1	2.2	cytochrome c release in cells expressing either fALS-SOD1s or wild-type SOD1 ETNA cells were transfected with cDNA coding for GFP-SOD1s fusion
16046141	SOD1	SOD1s	1.7	tag does not affect the dismutase activity of the various SOD1s ( Fig 4 A GFP-G93A and GFP-A4V mutants are similar
16046141	SOD1	SOD1s	1.7	As shown in Fig 4 C overexpression of mutant SOD1s causes the appearance of large intracellular aggregates (not not visible
16046141	SOD1	SOD1	2.2	large intracellular aggregates (not not visible in cells overexpressing wild-type SOD1 in ETNA cells as in various other experimental paradigms (
16046141	SOD1	SOD1s	1.7	not shown are not affected by the expression of mutant SOD1s in this system
16046141	SOD1	SOD1s	1.7	On the opposite cotransfection of mutant SOD1s with Apaf1 in ETNA_amp_#x2212;/_amp_#x2212; ETNA_amp_#x2212 _amp_#x2212 cells significantly restores the
16046141	SOD1	SOD1	2.2	Again protein oxidation induced by mutant SOD1 in ETNA+/+ ETNA cells is significantly reduced in cells lacking
16046141	SOD1	SOD1	2.2	has been suggested also by studies where targeting of mutant SOD1 specifically to the nucleus cytosol and in the mitochondrion matrix
16046141	SOD1	SOD1	2.2	classic_amp_#x201d apoptosis is involved in the motor neuron death in SOD1 mutant mice and perhaps also in ALS patients
16046141	SOD1	SOD1s	1.7	contribution of Apaf1 to cell death induced by different mutants SOD1s
16046141	SOD1	SOD1	2.2	loops (G37R, G37R I113T thus representing every class of mutant SOD1 found in patients except those truncated at the C-term end
16046141	SOD1	SOD1s	1.7	of neuronal origin and modulating the expression of both mutant SOD1s and Apaf1 we have observed that indeed Apaf1 is a
16046141	SOD1	SOD1	2.2	direct consequence of the postulated pro-oxidant toxic function of mutant SOD1 ( Valentine 2002
16046141	SOD1	SOD1	2.2	Mutant SOD1 may either exert some aberrant chemistry specifically inside (or or
16046141	SOD1	SOD1	2.2	Indeed the intracellular localization of wild-type and mutant SOD1 has recently been questioned
16046141	SOD1	SOD1	2.2	previous studies reporting that a fraction of the normally cytosolic SOD1 protein is detected within the mitochondrion probably either at the
16046141	SOD1	SOD1	2.2	al have reported that multiple disease-causing mutants but not wild-type SOD1 are recruited to mitochondria but only in affected tissues (
16046141	SOD1	SOD1	2.2	of protein are successfully imported but nearly constant amounts of SOD1 mutants and covalently damaged adducts of them accumulate
16046141	SOD1	SOD1	2.2	damage from action of spinal cord-specific factors that recruit mutant SOD1 to spinal mitochondria as the basis for their selective toxicity
16046141	SOD1	SOD1	2.2	to being in the mitochondrial outer membrane and intermembrane space SOD1 is also localized in the mitochondrial matrix
16046141	SOD1	SOD1	2.2	Furthermore aberrant SOD1 macromolecular aggregates are formed in the matrix of brain mitochondria
16046141	SOD1	SOD1s	1.7	Aggregation of mitochondrial mutant SOD1s may also have a role in altering the functionality of
16046141	SOD1	SOD1	2.2	These results suggest a mechanism by which mutant SOD1 can disrupt the association of proteins involved in cell survival
16046141	SOD1	SOD1	2.2	causes altering mitochondria functionality or from abnormal aggregation of wild-type SOD1 together with mitochondria proteins
16046141	SOD1	SOD1	2.2	(A) A Western blot analysis of SOD1 expression in SH-SY5Y cells untransfected or transiently transfected for 48
16046141	SOD1	SOD1	2.2	h with wtSOD1 and G93A G37R G85R and I113T mutant SOD1 20 _amp_#x3bc g of total cell lysates was loaded
16046141	SOD1	SOD1	2.2	of total cell lysates was analyzed for the expression of SOD1 and Apaf1
16046141	SOD1	SOD1	2.2	After 24 h SOD1 activity was detected on 10% polyacrylamide gel by the NBT/riboflavin
16050975	SOD1	SOD1	3.5	of familial ALS expressing mutant Cu Zn superoxide dismutase (SOD1) SOD1
16050975	SOD1	SOD1	3.5	Although the mechanisms whereby mutant SOD1 damages mitochondria remain to be fully understood the finding that
16050975	SOD1	SOD1	3.5	be fully understood the finding that a portion of mutant SOD1 is localized in mitochondria where it forms aberrant aggregates and
16050975	SOD1	SOD1	3.5	to devise models to better understand the effects of mutant SOD1 in mitochondria and the relative contribution of mitochondrial dysfunction to
16050975	SOD1	SOD1	3.5	Familial ALS due to SOD1 mutations and transgenic mouse models
16050975	SOD1	SOD1	3.5	to mutations in the gene encoding superoxide dismutase 1 (SOD1; SOD1 Cu Zn dismutase MIM147450 ( Rosen et al. 1993
16050975	SOD1	SOD1	3.5	SOD1 is a ubiquitous metalloprotein that prevents damage by oxygen-mediated free
16050975	SOD1	SOD1	3.5	The symptoms and pathology of FALS patients with SOD1 mutations closely resemble those of patients with SALS and the
16050975	SOD1	SOD1	3.5	and pathologic alterations in motor neurons from mice expressing mutant SOD1 are also strikingly similar to those found in SALS patients
16050975	SOD1	SOD1	3.5	Since the initial report of SOD1 mutations ( Rosen et al. 1993 more than 100 different
16050975	SOD1	SOD1	3.5	al. 1993 more than 100 different mutated forms of the SOD1 gene most of which are missense mutations have been identified
16050975	SOD1	SOD1	3.5	Because several pathogenic mutations do not affect SOD1 activity significantly ( Borchelt et al. 1994 a toxic _amp_#x2018
16050975	SOD1	SOD1	3.5	confirmed by several transgenic studies in which mice expressing mutant SOD1 develop motor neuron degeneration despite an overall increase in their
16050975	SOD1	SOD1	3.5	develop motor neuron degeneration despite an overall increase in their SOD1 activity ( Xu 2000
16050975	SOD1	SOD1	3.5	Mutant SOD1 is expressed ubiquitously but the pathological process leading to the
16050975	SOD1	SOD1	3.5	The tissue selectivity of SOD1 toxicity is a puzzling problem that has yet to be
16050975	SOD1	SOD1	3.5	While mouse models that express mutant SOD1 ubiquitously (similar similar to what happens in humans develop motor
16050975	SOD1	SOD1	3.5	develop motor neuron degeneration and ALS models that express mutant SOD1 exclusively either in the motor neurons or in astrocytes do
16050975	SOD1	SOD1	3.5	this view in chimeric mice that contain a mixture of SOD1 mutant and wild type cells motor neurons with wild type
16050975	SOD1	SOD1	3.5	mutant and wild type cells motor neurons with wild type SOD1 develop signs of degeneration whereas non-neuronal cells with wild type
16050975	SOD1	SOD1	3.5	to attenuate the degeneration of motor neurons with the mutant SOD1 gene ( Clement et al. 2003
16050975	SOD1	SOD1	3.5	However thanks to the availability of the mutant SOD1 transgenic mice that have provided an excellent platform to investigate
16050975	SOD1	SOD1	3.5	neuron degeneration in models of FALS caused by mutations in SOD1 gene
16050975	SOD1	SOD1	3.5	Mitochondrial involvement in models of ALS created by introduction of SOD1 mutants
16050975	SOD1	SOD1	3.5	A striking pathological feature observed in transgenic mice expressing SOD1 mutants G93A or G37R is the presence of membrane bound
16050975	SOD1	SOD1	3.5	evidence obtained in cellular models indicate that expression of mutant SOD1 is not only associated with mitochondrial morphological changes but also
16050975	SOD1	SOD1	3.5	observed in neuroblastoma cells transfected with the mutated form of SOD1
16050975	SOD1	SOD1	3.5	found in cultured motor neuron-like cells expressing mutated forms of SOD1 ( Menzies et al. 2002
16050975	SOD1	SOD1	3.5	reported that mitochondrial bioenergetics is impaired in the G93A mutant SOD1 mouse model of FALS
16050975	SOD1	SOD1	3.5	Recently we have found that the bioenergetic failure in the SOD1 mutant mice causes an impairment of mitochondrial calcium loading capacity
16050975	SOD1	SOD1	3.5	Impaired mitochondrial calcium loading capacity in SOD1 mutant mice may produce two consequences
16050975	SOD1	hSOD1	1.7	Consistent with this view antioxidant agents extended survival of mutant hSOD1 transgenic mice ( Jung et al. 2001 and Wu et
16050975	SOD1	SOD1	3.5	The expression of mutant SOD1 predisposes cultured neuronal cells to activation of apoptosis in response
16050975	SOD1	SOD1	3.5	3 are activated sequentially in differentiated neuroblastoma cells expressing mutant SOD1 in response to oxidative stress ( Pasinelli et al. 1998
16050975	SOD1	SOD1	3.5	1997 slow motor neuron degeneration and extend the survival of SOD1 mutant mice
16050975	SOD1	SOD1	3.5	For example mutant SOD1 mice genetically lacking caspase 11 an upstream regulator of the
16050975	SOD1	SOD1	3.5	Mechanisms of mitochondrial dysfunction in SOD1 FALS mitochondrial localization of SOD1
16050975	SOD1	SOD1	3.5	Mechanisms of mitochondrial dysfunction in SOD1 FALS mitochondrial localization of SOD1
16050975	SOD1	SOD1	3.5	changes and the biochemical abnormalities observed in mice expressing mutant SOD1 are still the object of intense investigation
16050975	SOD1	SOD1	3.5	Two fundamental questions remain to be answered how is mutant SOD1 causing mitochondrial degeneration and dysfunction and is mitochondrial dysfunction necessary
16050975	SOD1	SOD1-induced	1.7	necessary and/or and or sufficient for the development of mutant SOD1-induced motor neuron degeneration
16050975	SOD1	SOD1	3.5	answering these questions is the finding that a portion of SOD1 (most most of which is cytosolic is actually localized in
16050975	SOD1	SOD1	3.5	SOD1 enzymatic activity in rat liver mitochondria was first detected by
16050975	SOD1	SOD1	3.5	Recently the existence of SOD1 in mitochondria of eukaryotic cells has been confirmed by several
16050975	SOD1	SOD1	3.5	By cell fractionation and mitochondrial purification techniques SOD1 was detected in the mitochondria of the yeast S cerevisiae
16050975	SOD1	SOD1	3.5	2001 and Higgins et al. 2002 have independently demonstrated that SOD1 localizes in the mitochondria of motor neurons in the spinal
16050975	SOD1	SOD1	3.5	These investigators showed that both wild type and mutant SOD1 are localized in mitochondria
16050975	SOD1	SOD1	3.5	addition Field and colleagues have showed that the retention of SOD1 inside yeast mitochondria is dependent upon the interaction with its
16050975	SOD1	SOD1	3.5	dependent upon the interaction with its copper chaperone CCS since SOD1 mutants that are unable to interact with CCS _amp_#x2018 leak
16050975	SOD1	SOD1	3.5	Based on mitochondrial fractionation experiments several groups have proposed that SOD1 concentrates mostly in the intermembrane space of mitochondria ( Okado-Matsumoto
16050975	SOD1	SOD1	3.5	Recent experiments suggest that in mice expressing transgenic human SOD1 a portion of mutant SOD1 may also localize in the
16050975	SOD1	SOD1	3.5	in mice expressing transgenic human SOD1 a portion of mutant SOD1 may also localize in the matrix space of mitochondria where
16050975	SOD1	SOD1	3.5	matrix space of mitochondria where it forms large aggregates containing SOD1 and possibly other mitochondrial matrix proteins ( Vijayvergiya and Manfredi
16050975	SOD1	SOD1	3.5	Although how mutant SOD1 damages mitochondria has not been unequivocally defined several non-mutually exclusive
16050975	SOD1	SOD1	3.5	Higgins and colleagues have observed that SOD1 and cytochrome c a resident protein of the intermembrane space
16050975	SOD1	SOD1	3.5	colocalize at the early stages of mitochondrial vacuolization in mutant SOD1 transgenic mice
16050975	SOD1	SOD1	3.5	They also observed large aggregates of SOD1 immunoreactive material within the vacuoles
16050975	SOD1	SOD1	3.5	and colleagues have recently reported that in transgenic mice mutant SOD1 but not wild type SOD1 associates preferentially with mitochondria of
16050975	SOD1	SOD1	3.5	that in transgenic mice mutant SOD1 but not wild type SOD1 associates preferentially with mitochondria of the spinal cord
16050975	SOD1	SOD1	3.5	They proposed that mutant SOD1 progressively accumulates and aggregates on the outer membrane causing _amp_#x2018
16050975	SOD1	SOD1	3.5	of FALS it would suggest that mitochondrial localization of mutant SOD1 resulting in protein import impairment is an important contributor to
16050975	SOD1	SOD1	3.5	mentioned above where both wild type and mutant transgenic human SOD1 were detected in the mitochondria of various tissues including brain
16050975	SOD1	SOD1	3.5	Discrepancies in terms of the localization of the wild type SOD1 in these studies may be attributed to the differences in
16050975	SOD1	SOD1	3.5	to the differences in the strategies for mitochondrial purification and SOD1 detection and will require further experiments to be reconciled
16050975	SOD1	SOD1	3.5	to clarify the specificity and the exact intramitochondrial localization of SOD1 there is general agreement that mutant SOD1 tends to form
16050975	SOD1	SOD1	3.5	intramitochondrial localization of SOD1 there is general agreement that mutant SOD1 tends to form aggregates in mitochondria with potential pathogenic effects
16050975	SOD1	SOD1	3.5	In particular it will be interesting to assess whether mutant SOD1 forms abnormal interactions with other mitochondrial proteins which may lead
16050975	SOD1	SOD1	3.5	such potentially harmful protein-protein interactions is the binding of mutant SOD1 with Bcl-2 ( Pasinelli et al. 2004
16050975	SOD1	SOD1	3.5	in protein import and energy metabolism may interact with mutant SOD1
16050975	SOD1	SOD1	3.5	Because SOD1 is present both in the cytosol and in mitochondria it
16050975	SOD1	SOD1	3.5	mitochondrial dysfunction to a direct toxic effect of mitochondrial mutant SOD1 alone
16050975	SOD1	SOD1	3.5	mitochondrial dysfunction may arise as a consequence of cytosolic mutant SOD1 toxicity cannot be ruled out
16050975	SOD1	SOD1	3.5	For example mutant cytosolic SOD1 could promote aberrant production of reactive oxygen species ( Estevez
16050975	SOD1	SOD1	3.5	are prominent pathological features in the G93A and the G37R SOD1 transgenic mice other mouse models such as those transgenic for
16050975	SOD1	SOD1	3.5	It remains to be tested whether some SOD1 mutants can affect mitochondrial functions without causing overt morphological changes
16050975	SOD1	SOD1	3.5	Since most of the work on the bioenergetics of SOD1 mutant mitochondria has been done in the G93A model in
16050975	SOD1	SOD1	3.5	function and protecting mitochondria from the pro-apoptotic effect of mutant SOD1
16050975	SOD1	SOD1	3.5	of the mitochondrial apoptotic pathway extend the lifespan of mutant SOD1 transgenic mice
16050975	SOD1	SOD1	3.5	could be to generate cellular and animal models where mutant SOD1 is selectively localized in the mitochondria
16050975	SOD1	SOD1	3.5	Mitochondrial targeting of SOD1 could be achieved by appending specific mitochondrial targeting signals on
16050975	SOD1	SOD1	3.5	Conversely the identification of protein domains in SOD1 crucial for its mitochondrial import could allow for the generation
16050975	SOD1	SOD1	3.5	the generation of models where the mitochondrial content of mutant SOD1 is drastically reduced or eliminated
16050975	SOD1	SOD1	3.5	The comparison of these models with the ones where mutant SOD1 is expressed in both the cytosolic and mitochondrial compartments will
16050975	SOD1	SOD1	3.5	compartments will help us defining the role that mitochondrial mutant SOD1 plays in mitochondrial dysfunction and ultimately in the pathogenesis of
16050975	SOD1	SOD1-related	1.7	Fig 1._amp_#xa0 Diagram of potential pathways of mitochondrial involvement in SOD1-related ALS
16050975	SOD1	SOD1	3.5	Mutant SOD1 has been proposed to affect mitochondrial functions in several ways
16050975	SOD1	SOD1	3.5	Mutant SOD1 may affect mitochondria directly within the organelles or indirectly from
16050975	SOD1	SOD1	3.5	Within mitochondria mutant SOD1 may interfere with the anti-apoptotic function of Bcl-2 ( Pasinelli
16188953	SOD1	SOD1	2.2	cases are caused by mutations in superoxide dismutase 1 (SOD1), SOD1 which expressed in mice result in a phenotype resembling the
16188953	SOD1	SOD1	2.2	Transgenic SOD1 mice represent the predominant model to study ALS pathogenesis and
16188953	SOD1	SOD1	2.2	test for neuroprotection by PPX/SND PPX SND in vivo transgenic SOD1 mice were treated with both compounds
16188953	SOD	SOD-catalase	2.2	PPX (300 300 microM malonate (Malo, Malo 10 mM the SOD-catalase mimic EUK-134 (Melov Melov et al. 2001 EUK (30 30
16188953	SOD	SOD	2.2	The specificity for hydrogen peroxide was verified with SOD (300 300 mU/ml), mU ml which did not affect the
16188953	SOD	SOD-catalase-mimetic	2.2	and compartments obtained efficacies were compared with EUK-134 a potent SOD-catalase-mimetic (Jung Jung et al. 2001 Melov et al. 2001
16188953	SOD1	SOD1	2.2	Treatment of SOD1(G93A) SOD1 G93A transgenic mice with PPX and SND
16188953	SOD	SOD-catalase	2.2	SND and compared the obtained efficacy with EUK-134 a potent SOD-catalase mimetic (Melov Melov et al. 2001
16188953	SOD1	SOD1	2.2	Consequently we tested both compounds in mice expressing the G93A-mutant SOD1 a common and well described model of ALS where neuronal
16188953	SOD1	SOD1	2.2	Additionally survival time in SND-treated SOD1 (G93A) G93A mice (132 132 _amp_#177 2 days mean _amp_#177
16227974	SOD1	SOD1	1.4	the cytosolic form of the antioxidant protein superoxide dismutase ( SOD1 1
16227974	SOD1	SOD1	1.4	That said how disease-causing mutations in SOD1 lead to ALS remains controversial 2 3
16227974	SOD1	SOD1	1.4	ATM JunD parkin peroxiredoxin I PINK1 Ras seladin-1 SIRT1 SIRT3 SOD1
16624679	SOD1	SOD1	3.7	G93A Cu/Zn Cu Zn superoxide dismutase (SOD1), SOD1 a human mutant SOD1 associated with familial amyotrophic lateral sclerosis
16624679	SOD1	SOD1	3.7	Cu/Zn Cu Zn superoxide dismutase (SOD1), SOD1 a human mutant SOD1 associated with familial amyotrophic lateral sclerosis increased the toxicity of
16624679	SOD1	SOD1	3.7	have mutant forms of Cu/Zn Cu Zn superoxide dismutase (SOD1), SOD1 a free radical-scavenging enzyme that converts the superoxide anion radical
16624679	SOD1	SOD1	3.7	Apparently the motor neuron toxicity of mutant SOD1 is due to a _amp_#x201c gain of function(s)_amp_#x201d; function s
16624679	SOD1	SOD1	3.7	oxidative chemistry and/or and or misfolding and aggregation of mutant SOD1 11
16624679	SOD1	SOD1	3.7	The identification of SOD1 mutations as a cause of ALS has served for creating
16624679	SOD1	SOD1	3.7	experimental models of the disease expressing mutant forms of human SOD1 in laboratory animals and cells
16624679	SOD1	SOD1	3.7	conversion more in NSC-34 motoneuronal cells expressing mutant (G93A) G93A SOD1 than in those expressing wild-type (wt) wt SOD1
16624679	SOD1	SOD1	3.7	(G93A) G93A SOD1 than in those expressing wild-type (wt) wt SOD1
16624679	SOD1	SOD1	3.7	stably expressing wild-type (wt) wt or mutant (G93A) G93A human SOD1 were generated and checked for SOD1 expression as previously described
16624679	SOD1	SOD1	3.7	mutant (G93A) G93A human SOD1 were generated and checked for SOD1 expression as previously described 43
16624679	SOD1	SOD1	3.7	lines stably transfected with cDNAs of human wt/G93A wt G93A SOD1 were generated
16624679	SOD1	SOD1	3.7	Western blotting indicated similar levels of murine SOD1 protein in all the lines wt or the G93A mutant
16624679	SOD1	SOD1	3.7	lines wt or the G93A mutant form of the human SOD1 protein was expressed at comparable levels ( Fig 2
16624679	SOD1	SOD1	3.7	The greater susceptibility of cells transfected with G93A SOD1 to inhibition of complex I of the ETC persisted after
16624679	SOD1	SOD1	3.7	To see why the presence of G93A SOD1 increased the motor neuron cells_amp_#x2019 susceptibility to rotenone we considered
16624679	SOD1	SOD1	3.7	toxin for motor neurons of humans with mutant forms of SOD1 and for unraveling the toxicity of these mutant forms
16624679	SOD1	SOD1	3.7	in the toxic _amp_#x201c gain of function_amp_#x201d of mutant SOD1(s) SOD1 s 11 free radical scavengers were protective in several models
16624679	SOD1	SOD1	3.7	might affect the mitochondria is reinforced by the finding that SOD1 also localizes in the mitochondrial intermembrane space and matrix 39
16624679	SOD1	SOD1	3.7	space and matrix 39 48 and 51 and that mutant SOD1 forms aggregates in the matrix 51
16624679	SOD1	SOD1	3.7	of mitochondrial membrane potential 45 and 49 was trapped by SOD1 aggregates in spinal cord mitochondria of transgenic SOD1 mice and
16624679	SOD1	SOD1	3.7	trapped by SOD1 aggregates in spinal cord mitochondria of transgenic SOD1 mice and in spinal cord homogenates from human samples 40
16624679	SOD1	SOD1	3.7	factor for motor neurons of individuals carrying the mutant G93A SOD1 and might act in concert with other genetic defects associated
16624679	SOD1	SOD1	3.7	SOD1 is present in the cytosol and in the mitochondrial intermembrane
16624679	SOD1	SOD1	3.7	Fig 2._amp_#xa0 Expression of human SOD1 in the NSC-34 cellular model of FALS
16624679	SOD1	SOD1	3.7	lane 2 human wild-type (lane lane 3 or G93A mutant SOD1 (lane lane 4 was done using a polyclonal anti-human SOD1
16624679	SOD1	SOD1	3.7	SOD1 (lane lane 4 was done using a polyclonal anti-human SOD1 antibody that crossreacts with murine SOD1(mSOD1) SOD1 mSOD1
16624679	SOD1	SOD1	3.7	a polyclonal anti-human SOD1 antibody that crossreacts with murine SOD1(mSOD1) SOD1 mSOD1
16624679	SOD1	mSOD1	2.7	polyclonal anti-human SOD1 antibody that crossreacts with murine SOD1(mSOD1) SOD1 mSOD1
16624679	SOD1	mSOD1	2.7	The positions of mSOD1 and human SOD1(hSOD1) SOD1 hSOD1 are indicated in SDS-PAGE they
16624679	SOD1	SOD1	3.7	The positions of mSOD1 and human SOD1(hSOD1) SOD1 hSOD1 are indicated in SDS-PAGE they can be resolved into
16624679	SOD1	hSOD1	2.7	The positions of mSOD1 and human SOD1(hSOD1) SOD1 hSOD1 are indicated in SDS-PAGE they can be resolved into two
16624679	SOD1	mSOD1	2.7	resolved into two bands due to the faster migration of mSOD1
16681429	SOD	SOD	1.9	activity of the following ADEs copper-zinc superoxide dismutase (CuZn CuZn SOD catalase (CAT), CAT glutathione peroxidase (GSH-Px) GSH-Px and glutathione reductase
16681429	SOD1	SOD1	3.4	- familial ALS patients with the Leu144Phe mutation in the SOD1 gene FALS (+/+)], asymptomatic carriers with the Leu144Phe mutation in
16681429	SOD1	SOD1	3.4	FALS (+/+)], asymptomatic carriers with the Leu144Phe mutation in the SOD1 gene (+/-), - and control subjects (-/-) - -
16681429	SOD	SOD	1.9	the in vitro effect of diethyldithiocarbamate (DDC) DDC on CuZn SOD activity in erythrocytes from FALS patients SALS patients and control
16681429	SOD1	SOD1	3.4	The SOD1 gene mutation decreased CuZn SOD and GSH-Px activity (two-way two-way
16681429	SOD	SOD	1.9	The SOD1 gene mutation decreased CuZn SOD and GSH-Px activity (two-way two-way ANOVA significant mutation effect
16681429	SOD	SOD	1.9	We noted that the disease also contributed to decreased CuZn SOD activity in SALS patients in comparison with the control group
16681429	SOD	SOD	1.9	Finally DDC inhibited CuZn SOD activity in erythrocytes from control subjects FALS (Leu144Phe) Leu144Phe patients
16877542	ALS	ALS	2.2	Abstract ALS is a fatal paralytic disorder characterized by a progressive loss
16877542	ALS	ALS	2.2	species-producing enzyme during inflammation is activated in spinal cords of ALS patients and in spinal cords in a genetic animal model
16877542	ALS	ALS	2.2	We demonstrate that inactivation of NADPH oxidase in ALS mice delays neurodegeneration and extends survival
16877542	ALS	ALS	2.2	death and contribute to the selective motor neuronal degeneration in ALS
16877542	ALS	ALS	2.2	Keywords Akt ALS microglia oxidation non-cell autonomous
16877542	SOD1	SOD1	2.2	Transgenic SOD1 G93A mice [C57BL/6J-TgN(SOD1-G93A)1Gur C57BL 6J-TgN SOD1-G93A 1Gur dl were crossed
16877542	SOD1	SOD1	2.2	for details about the timeline of behavioral abnormalities in transgenic SOD1 G93A mice
16877542	ALS	ALS	2.2	60.5 _amp_#x000b1 10.2 years and 8.0 _amp_#x000b1 2.6 h respectively ALS group ( n = 6 60.5 _amp_#x000b1 4.2 years and
16877542	ALS	ALS	2.2	For the ALS patients the mean duration of disease was 19.3 _amp_#x000b1 2.6
16877542	ALS	ALS	2.2	NADPH Oxidase Is Up-Regulated in Inflamed Spinal Cords of ALS Mice
16877542	SOD1	SOD1	2.2	stages of the disease in transgenic mice expressing mutant human SOD1 with a substitution of glycine to alanine in position 93
16877542	SOD1	SOD1	2.2	a substitution of glycine to alanine in position 93 (SOD1 SOD1 G93A the most widely studied model of ALS
16877542	ALS	ALS	2.2	93 (SOD1 SOD1 G93A the most widely studied model of ALS
16877542	ALS	ALS	2.2	cord which carries the brunt of the pathology in this ALS model was determined by analyzing its catalytic subunit gp91 phox
16877542	SOD1	SOD1	2.2	whole-tissue extracts of spinal cord rose over time in transgenic SOD1 G93A mice ( Fig 1 A B D and E
16877542	SOD1	SOD1	2.2	in membrane fractions of spinal cord extracts from symptomatic transgenic SOD1 G93A mice ( Fig 1 C indicating that this cytosolic
16877542	SOD1	SOD1	2.2	Histological evaluation of the spinal cord of symptomatic transgenic SOD1 G93A mice showed numerous gp91 phox -positive cells primarily in
16877542	SOD1	SOD1	2.2	NADPH Oxidase Causes Protein Oxidation in Transgenic SOD1 G93A Mice
16877542	SOD1	SOD1	2.2	characterized the status of spinal cord NADPH oxidase in transgenic SOD1 G93A mice by probing for formation of ROS and evidence
16877542	SOD1	SOD1	2.2	In contrast in symptomatic transgenic SOD1 G93A mice carrying the wild-type gp91 phox allele (SOD SOD
16877542	SOD	SOD	2.2	SOD1 G93A mice carrying the wild-type gp91 phox allele (SOD SOD G93A /gp91 gp91 phox spinal cord ethidium fluorescence was intense
16877542	SOD1	SOD1	2.2	In symptomatic transgenic SOD1 G93A mice carrying the nonfunctional mutant allele (SOD SOD G93A
16877542	SOD	SOD	2.2	transgenic SOD1 G93A mice carrying the nonfunctional mutant allele (SOD SOD G93A /gp91 gp91 phox_amp_#x02212 ( 12 spinal cord ethidium fluorescence
16877542	SOD1	SOD1	2.2	Symptomatic transgenic SOD1 G93A /gp91 gp91 phox mice but not age-matched SOD1 G93A
16877542	SOD1	SOD1	2.2	transgenic SOD1 G93A /gp91 gp91 phox mice but not age-matched SOD1 G93A /gp91 gp91 phox_amp_#x02212 mice had increased levels of spinal
16877542	SOD1	SOD1	2.2	for protein carbonyl adducts occurred in spinal cord sections from SOD1 G93A /gp91 gp91 phox mice at the level of cells
16877542	ALS	ALS	2.2	NADPH Oxidase Induction and Neuronal Protein Carbonylation in Sporadic ALS
16877542	SOD1	SOD1	2.2	to determine whether the NADPH oxidase alterations identified in transgenic SOD1 G93A mice were also present in human sporadic ALS the
16877542	ALS	ALS	2.2	transgenic SOD1 G93A mice were also present in human sporadic ALS the most common form of the disease ( 1
16877542	ALS	ALS	2.2	was _amp_#x02248 3-fold higher and its immunoreactivity robust in sporadic ALS spinal cords ( Fig 2 E
16877542	ALS	ALS	2.2	2 F and were identified in all of the typical ALS loci of neurodegeneration including the anterior horn and the lateral
16877542	ALS	ALS	2.2	protein carbonyl adducts in postmortem spinal cord sections from sporadic ALS cases which seemed to be mainly associated with large motor
16877542	ALS	ALS	2.2	for protein carbonyl adducts per lumbar spinal cord section in ALS patients whereas no such immunoreactive motor neurons were seen in
16877542	SOD1	SOD1	2.2	Deletion of gp91 phox Mitigates the Disease Phenotype in Transgenic SOD1 G93A Mice
16877542	SOD1	SOD1	2.2	of NADPH oxidase activation on the disease phenotype in the SOD1 G93A mouse model of ALS
16877542	ALS	ALS	2.2	the disease phenotype in the SOD1 G93A mouse model of ALS
16877542	SOD1	SOD1	2.2	Transgenic SOD1 G93A /gp91 gp91 phox_amp_#x02212 mice reached end-stage paralysis (defined defined
16877542	SOD1	SOD1	2.2	a loss of the righting reflex later than their transgenic SOD1 G93A /gp91 gp91 phox counterparts ( Fig 3 A which
16877542	SOD1	SOD1	2.2	3 A which resulted in a longer lifespan of transgenic SOD1 G93A /gp91 gp91 phox_amp_#x02212 mice (log-rank log-rank test = 15.3
16877542	SOD1	SOD1	2.2	Compared with end-stage transgenic SOD1 G93A /gp91 gp91 phox mice age-matched transgenic SOD1 G93A /gp91
16877542	SOD1	SOD1	2.2	end-stage transgenic SOD1 G93A /gp91 gp91 phox mice age-matched transgenic SOD1 G93A /gp91 gp91 phox_amp_#x02212 mice had _amp_#x02248 50% more anterior
16877542	SOD1	SOD1	2.2	the glial cytokine IL-1_amp_#x003b2 did not differ between age-matched transgenic SOD1 G93A /gp91 gp91 phox mice and SOD1 G93A /gp91 gp91
16877542	SOD1	SOD1	2.2	between age-matched transgenic SOD1 G93A /gp91 gp91 phox mice and SOD1 G93A /gp91 gp91 phox_amp_#x02212 mice (Fig Fig 7 which is
16877542	SOD1	SOD1	2.2	the deficit of gp91 phox were the levels of human SOD1 in transgenic SOD1 G93A mice (Fig Fig 7 or the
16877542	SOD1	SOD1	2.2	gp91 phox were the levels of human SOD1 in transgenic SOD1 G93A mice (Fig Fig 7 or the size of muscle
16877542	SOD1	SOD1	2.2	Insulin-Like Growth Factor 1 (IGF1)/Akt IGF1 Akt Pathway in Transgenic SOD1 G93A Mice
16877542	ALS	ALS	2.2	explored whether NADPH oxidase-mediated protein modifications might promote neurodegeneration in ALS by damaging essential surviving pathways for motor neurons such as
16877542	SOD1	SOD1	2.2	kinase cognate receptor in the spinal cord of symptomatic transgenic SOD1 G93A /gp91 gp91 phox mice ( Fig 4 A and
16877542	SOD1	SOD1	2.2	receptor signaling ( 15 did not differ between symptomatic transgenic SOD1 G93A mice and their nontransgenic littermates
16877542	ALS	ALS	2.2	molecular pathway is not oxidatively modified by inflammation in this ALS model
16877542	SOD1	SOD1	2.2	Although mutant SOD1 is expressed in all cells markers of IGF1 transduction such
16877542	SOD1	SOD1	2.2	smaller glia-like cells in spinal cord sections of symptomatic transgenic SOD1 G93A mice
16877542	SOD1	SOD1	2.2	phospho-IGF1 receptor-immunoreactive cells in spinal cord sections from symptomatic transgenic SOD1 G93A /gp91 gp91 phox mice than from age-matched SOD1 G93A
16877542	SOD1	SOD1	2.2	transgenic SOD1 G93A /gp91 gp91 phox mice than from age-matched SOD1 G93A /gp91 gp91 phox_amp_#x02212 mice ( Fig 4 C _amp_#x02013
16877542	SOD1	SOD1	2.2	ratios ( Fig 4 K and L in symptomatic transgenic SOD1 G93A /gp91 gp91 phox mice compared with their age-matched SOD1
16877542	SOD1	SOD1	2.2	SOD1 G93A /gp91 gp91 phox mice compared with their age-matched SOD1 G93A /gp91 gp91 phox_amp_#x02212 counterparts
16877542	SOD1	SOD1	2.2	idea that oxidative modification of IGF1 receptor in symptomatic transgenic SOD1 G93A /gp91 gp91 phox mice is associated with a range
16877542	ALS	ALS	2.2	Experimental evidence supports a model for ALS neurodegeneration in which nonneuronal cells such as microglia contribute to
16877542	SOD1	SOD1	2.2	Conversely in transgenic SOD1 G93A mice paralleling the worsening of the ALS phenotype there
16877542	ALS	ALS	2.2	in transgenic SOD1 G93A mice paralleling the worsening of the ALS phenotype there was an intensification of spinal cord microgliosis accompanied
16877542	ALS	ALS	2.2	of oxidatively damaging nearby macromolecules and cells homed within inflamed ALS tissues
16877542	SOD1	SOD1	2.2	were markedly elevated in spinal cord extracts of symptomatic transgenic SOD1 G93A mice for the most part in a NADPH oxidase-dependent
16877542	ALS	ALS	2.2	was also found in postmortem spinal cords from human sporadic ALS cases ( Fig 2 supporting the conclusion that the occurrence
16877542	ALS	ALS	2.2	occurrence of inflammation-mediated oxidative damage is not restricted to familial ALS caused by SOD1 mutations but is also a pathological hallmark
16877542	SOD1	SOD1	2.2	oxidative damage is not restricted to familial ALS caused by SOD1 mutations but is also a pathological hallmark of the prevalent
16877542	ALS	ALS	2.2	a pathological hallmark of the prevalent nonfamilial sporadic form of ALS
16877542	SOD1	SOD1	2.2	of the gp91 phox subunit of NADPH oxidase in transgenic SOD1 G93A mice eliminates the production of microglial-derived ROS ( Fig
16877542	ALS	ALS	2.2	M and importantly prolongs survival and retards neurodegeneration in this ALS model ( Fig 3
16877542	SOD1	SOD1	2.2	Deletion of gp91 phox in transgenic SOD1 G93A mice did not alter the spinal cord microglial response
16877542	SOD1	SOD1	2.2	the spinal cord microglial response or the expression of human SOD1 in transgenic SOD1 G93A mice (Fig Fig 7 which is
16877542	SOD1	SOD1	2.2	microglial response or the expression of human SOD1 in transgenic SOD1 G93A mice (Fig Fig 7 which is a known determinant
16877542	ALS	ALS	2.2	which is a known determinant of disease severity in this ALS model ( 18
16877542	SOD1	SOD1	2.2	Consequently the attenuated phenotype seen in transgenic SOD1 G93A /gp91 gp91 phox_amp_#x02212 mice is attributable to the lack
16877542	SOD1	SOD1	2.2	either an impaired microglial response or expression of the human SOD1 G93A transgene
16877542	ALS	ALS	2.2	NADPH oxidase contributes to the degeneration of motor neurons in ALS
16877542	ALS	ALS	2.2	in the pathogenesis of chronic noninfectious pathological conditions such as ALS
16877542	SOD1	SOD1	2.2	magnitude of benefit afforded by gp91 phox deletion in transgenic SOD1 G93A mice argues that targeting neuroinflammation by inhibiting just one
16877542	ALS	ALS	2.2	not be sufficient to produce robust and lasting neuroprotection in ALS patients
16877542	ALS	ALS	2.2	However the chronic nature of ALS suggests that neuroinflammation is likely protracted and not as strong
16877542	ALS	ALS	2.2	oxidative stress with the selective demise of motor neurons in ALS
16877542	ALS	ALS	2.2	of those already compromised as motor neurons probably are in ALS
16877542	SOD1	SOD1	2.2	was impaired by a NADPH oxidase-dependent mechanism in symptomatic transgenic SOD1 G93A mice ( Fig 4
16877542	SOD1	SOD1	2.2	to withstand the toxicity of etiologic agents such as mutant SOD1
16877542	SOD1	SOD1	2.2	the spinal cord and enhances motor neuronal survival in transgenic SOD1 G93A mice ( 23
16877542	SOD1	SOD1	2.2	Nevertheless whether transgenic SOD1 G93A mice carrying the gp91 phox null mutation reach end-stage
16877542	SOD1	SOD1	2.2	Injection of transgenic SOD1 G93A mice with an adeno-associated virus carrying an IGF1 gene
16877542	ALS	ALS	2.2	may blunt the motor neuron survival response to IGF1 in ALS
16877542	ALS	ALS	2.2	Perhaps the modest change in ALS progression that is seen in patients treated with human recombinant
16877542	ALS	ALS	2.2	that optimal therapeutic response to IGF1 in diseases such as ALS may rely on a concomitant administration of this trophic factor
16877542	SOD1	SOD1	2.2	oxidase stimulates carbonylation of spinal cord motor neurons in transgenic SOD1 G93A mice
16877542	SOD1	SOD1	2.2	E in 1-month-old (asymptomatic) asymptomatic to 4-month-old (end-stage) end-stage transgenic SOD1 (more more ...
16877542	ALS	ALS	2.2	with motor neuron carbonylation in the spinal cord of sporadic ALS patients
16877542	ALS	ALS	2.2	spinal cord extracts from six normal controls and six age-matched ALS patients
16877542	SOD1	SOD1	2.2	of gp91 phox increases lifespan and lessens neurodegeneration in transgenic SOD1 G93A mice
16877542	SOD1	SOD1	2.2	( A Survival comparison of transgenic SOD1 G93A /gp91 gp91 phox mice (red) red (122.0 122.0 _amp_#x000b1
16877542	SOD1	SOD1	2.2	(122.0 122.0 _amp_#x000b1 1.7 days n = 19 and transgenic SOD1 G93A /gp91 gp91 phox_amp_#x02212 littermates (more more ...
16877542	SOD1	SOD1	2.2	ROS reactive oxygen species SOD1 superoxide dismutase 1 IGF1 insulin-like growth factor 1
16877542	ALS	ALS	2.2	ALS is the most common adult-onset paralytic disease and is characterized
16877542	SOD1	SOD1	2.2	dominant mutations in the gene for superoxide dismutase 1 (SOD1) SOD1 cause familial ALS ( 2 3
16877542	ALS	ALS	2.2	the gene for superoxide dismutase 1 (SOD1) SOD1 cause familial ALS ( 2 3
16877542	SOD1	SOD1	2.2	Overexpression of SOD1 mutants in rodents emulate clinical and pathological hallmarks of ALS
16877542	ALS	ALS	2.2	SOD1 mutants in rodents emulate clinical and pathological hallmarks of ALS through a toxic gain of function ( 4
16877542	SOD1	SOD1	2.2	mixture of neuronal and nonneuronal cells expressing wild-type or mutant SOD1 ( 5 investigation of these animals suggested that nonneuronal cells
16877542	SOD1	SOD1	2.2	Corroborating this hypothesis is the demonstration that reduction of mutant SOD1 selectively in microglia extended survival in transgenic SOD1 G37R mice
16877542	SOD1	SOD1	2.2	of mutant SOD1 selectively in microglia extended survival in transgenic SOD1 G37R mice ( 6
16877542	ALS	ALS	2.2	we undertook the study of NADPH oxidase in both human ALS and one of its genetic models
16877542	ALS	ALS	2.2	and mouse postmortem tissues indicate that spinal cord microgliosis in ALS is accompanied with an up-regulation of NADPH oxidase
16895581	SOD1	SOD1	2.7	either wild-type or mutant Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1
17014688	SOD1	SOD1	1.7	NSC-34 (2) 2 a genetic mouse model of ALS (SOD1(G93A)-transgenic SOD1 G93A -transgenic mice and (3) 3 a group of 31
17014688	SOD1	SOD1	1.7	In SOD1(G93A)-transgenic SOD1 G93A -transgenic mice high-dose oral melatonin delayed disease progression and
17099894	SOD1	mSOD1	1.4	The mechanisms of human mutant superoxide dismutase-1 (mSOD1) mSOD1 toxicity to motor neurons (MNs) MNs are unresolved
17099894	SOD1	mSOD1	1.4	swelling is associated with compromised Na K-ATPase activity and aggregation mSOD1 mouse MNs accumulate mitochondria from the axon terminals and generate
17099894	SOD1	mSOD1	1.4	subunit-I and alpha-synuclein as well as nitrated SOD2 accumulate in mSOD1 mouse spinal cord
17099894	SOD1	mSOD1	1.4	Mitochondria in mSOD1 mouse MNs accumulate NADPH diaphorase and inducible nitric oxide synthase
17099894	SOD1	mSOD1	1.4	as participants in the process of MN degeneration caused by mSOD1
17105868	SOD1	SOD1	2.4	G93A transgenic mice carrying the G93A human SOD1 mutation were obtained from the Jackson Laboratory (Bar Bar Harbor
17105868	SOD1	SOD1	2.4	These mechanisms include mitochondrial dysfunction SOD1 mutations and activation of Ca -permeable ionotropic glutamate receptors which
17105868	SOD1	SOD1	2.4	and point mutations in the Cu Zn superoxide dismutase ( SOD1 gene the last of which are present in approximately 20%
17105868	SOD1	SOD1	2.4	Two findings in particular suggest a strong link between the SOD1 gene mutation and oxidative stress
17105868	SOD1	SOD1	2.4	This raises the possibility that the SOD1 mutation not only enhances oxidative stress in lumbar motor neurons
17105868	SOD1	SOD1	2.4	The latter effect may be attributable to interaction of mutant SOD1 and Bcl-2 causing mitochondrial dysfunction and subsequently increased sensitivity to
17105868	SOD	SOD	1.9	DIV days in vitro BSO DL -buthionine- S R -sulfoximine SOD superoxide dismutase LDH lactate dehydrogenase FADD Fas-associated death domain
17150307	SOD1	SOD1	3.2	Mutations of Cu Zn-superoxide dismutase (SOD1) SOD1 gene cause motor neuron degeneration and have linked to 2_amp_#x02013
17150307	SOD1	SOD1	3.2	culture model it has been shown that expression of mutant SOD1 gene decreased cellular levels of GSH suggesting the reduction in
17150307	SOD1	SOD1-mediated	2.2	the reduction in GSH bioavailability may participate in the mutant SOD1-mediated motor neuron degeneration ( Lee et al. 2001
17150307	SOD	SOD	2.2	significantly treatment of ALS-like transgenic mice with antioxidants such as SOD and catalase mimetics ( Jung et al. 2001 DMPO (
17150307	SOD1	SOD1	3.2	Oxidized Glutathione MBM Monobromobimane PFA Paraformaldehyde ROS Reactive Oxygen Species SOD1 Cu Zn-Superoxide Dismutase TUNEL Terminal Deoxynucleotidyl Transferase-Mediated Nick End Labeling
17174478	SOD	SOD	3.4	reductase module NHEJ nonhomologous end joining ROS reactive oxygen species SOD superoxide dismutase SSBs single-strand breaks TC-NER transcription-coupled nucleotide excision repair
17174478	SOD	SOD	3.4	rapidly scavenged in the cell by the superoxide dismutase (SOD) SOD enzymes
17174478	SOD	SOD	3.4	SOD enzymes catalyze the disproportionation of superoxide anion radicals to molecular
17174478	SOD	SOD	3.4	The important role of SOD in the brain was highlighted by genetic inactivation of the
17174478	SOD	SOD	3.4	was highlighted by genetic inactivation of the mitochondrial form of SOD manganese SOD (MnSOD), MnSOD in mice
17174478	SOD	SOD	3.4	by genetic inactivation of the mitochondrial form of SOD manganese SOD (MnSOD), MnSOD in mice
17174478	SOD	SOD	3.4	Treatment with an SOD mimetic MnTBAP rescued the MnSOD _amp_#x02212;/_amp_#x02212; _amp_#x02212 _amp_#x02212 mutant mice
17174478	SOD1	SOD1	2.9	However mutations in the superoxide dismutase1 (SOD1) SOD1 gene give rise to approximately 20% of FALS cases (
17174478	SOD1	SOD1	2.9	SOD1 encodes a cytosolic copper zinc superoxide dismutase (Cu,Zn Cu Zn
17174478	SOD	SOD	3.4	encodes a cytosolic copper zinc superoxide dismutase (Cu,Zn Cu Zn SOD which similar to the mitochondrial MnSOD is responsible for the
17174478	SOD	SOD	3.4	Structural studies on human Cu Zn SOD have revealed that the enzyme is composed of two identical
17174478	SOD1	SOD1	2.9	A multitude of SOD1 mutations have been identified in FALS patients ( Gaudette et
17174478	SOD	SOD	3.4	The mutations are dispersed throughout the 153 amino acid residue SOD polypeptide ( Deng et al. 1993
17174478	SOD	SOD	3.4	data support the idea that toxicity of intracellular Cu Zn SOD aggregates may result from protein misfolding or impaired protein degradation
17174478	SOD	SOD	3.4	found in the cytoplasm are strongly immunoreactive to Cu Zn SOD antibodies and cannot be dissociated with strong detergents or reducing
17174478	SOD	SOD-mediated	2.9	One proposed mechanism of FALS mutant SOD-mediated toxicity is the coprecipitation of mutant Cu Zn SOD with
17174478	SOD	SOD	3.4	mutant SOD-mediated toxicity is the coprecipitation of mutant Cu Zn SOD with essential cellular components ( Bruijn et al. 1998 Johnston
17174478	SOD	SOD	3.4	and this has been demonstrated with the copper chaperone for SOD (CCS)( CCS Kato et al. 2001 nitric oxide synthase (NOS)
17174478	SOD	SOD	3.4	is not entirely clear how the many different Cu Zn SOD single-site mutations which are widely dispersed throughout the protein sequence
17174478	SOD	SOD	3.4	combined structural biochemical and biophysical characterizations of two FALS mutant SOD proteins ( DiDonato et al. 2003
17174478	SOD	SOD	3.4	two FALS proteins represent the two major structural classes of SOD mutations
17191135	SOD1	SOD1	1.9	antioxidant enzymatic activities such as GPx GSSG reductase CAT and SOD1 were also found elevated in several regions of AD brain
17368952	SOD1	SOD1	5.5	oxidation of proteins and mutation of Cu Zn-superoxide dismutase (SOD1) SOD1 in ALS
17368952	SOD1	mSOD1	2.7	Transgenic mice overexpressing the mutant Cu Zn-superoxide dismutase (mSOD1) mSOD1 gene from humans with familial ALS wild-type mice overexpressing the
17368952	SOD1	SOD1	5.5	humans with familial ALS wild-type mice overexpressing the normal human SOD1 gene and normal mice without gene overexpression were used
17368952	SOD1	mSOD1	2.7	Neurons containing nitrated and oxidized proteins were visualized only in mSOD1 mice in the motor cortex the cerebellar cortex and nucleus
17368952	SOD1	SOD1	5.5	This correlates mutation of SOD1 to nitration and oxidation of neurons in the movement regions
17368952	SOD1	mSOD1	2.7	the brain sections of both motor and sensory cortex in mSOD1 mice than in the corresponding regions of control mice (P=0.005
17368952	SOD1	SOD1	5.5	_amp_#x3c 0.001 further correlating nitration and oxidation of proteins to SOD1 mutation
17368952	SOD1	mSOD1	2.7	in the motor cortex than in the sensory cortex in mSOD1 mice (P=0.002 P=0.002 and 0.02 respectively indicating enhanced susceptibility of
17368952	SOD1	SOD1	5.5	in the brain tissues and in cerebrospinal fluid of mutant SOD1 mice
17368952	SOD1	SOD1	5.5	Our in vivo evidence correlates mutation of the SOD1 gene to increased nitric oxide nitration and oxidation of proteins
17368952	SOD1	SOD1	5.5	The discovery of mutation of the Cu Zn-superoxide dismutase (SOD1) SOD1 gene in familial ALS patients ( Deng et al 1993
17368952	SOD1	mSOD1	2.7	To explore how mutant Cu Zn-superoxide dismutase (mSOD1) mSOD1 causes ALS a transgenic mouse model was established by introducing
17368952	SOD1	SOD1	5.5	a human mutant (Gly Gly 93_amp_#x2192 Ala G93A of the SOD1 gene into the mouse ( Gurney et al. 1994 these
17368952	SOD1	SOD1	5.5	Since then over 100 different SOD1 mutants have been identified in ALS families and a number
17368952	SOD1	mSOD1	2.7	A gain of function hypothesis currently explains the neurotoxicity of mSOD1 by two mechanisms 1 mSOD1 directly promotes generation of reactive
17368952	SOD1	mSOD1	2.7	currently explains the neurotoxicity of mSOD1 by two mechanisms 1 mSOD1 directly promotes generation of reactive species and causes oxidative damage
17368952	SOD1	mSOD1	2.7	species and causes oxidative damage to major cellular components 2 mSOD1 aggregation with itself and other important proteins leads to toxicity
17368952	SOD	SOD	1.9	Superoxide dismutase (SOD) SOD is a major antioxidative defense enzyme converting superoxide anion (O
17368952	SOD1	mSOD1	2.7	Using mSOD1 transgenic models we previously demonstrated in vivo that mutation of
17368952	SOD1	SOD1	5.5	transgenic models we previously demonstrated in vivo that mutation of SOD1 elevates levels of H 2 O 2 _amp_#xb7 OH and
17368952	SOD1	SOD1	5.5	protein oxidation 8-hydroxy-2-deoxyguanosine_amp_#x2014 a marker of DNA oxidation compared with SOD1 and normal control (Nc) Nc mice ( Liu et al.
17368952	SOD1	SOD1	5.5	These results directly correlate mutation of SOD1 to generation of ROS and resulting oxidative damage
17368952	SOD	SOD	1.9	NO to form ONOO _amp_#x2212 which in turn reacts with SOD to form a nitronium-like intermediate that can nitrate tyrosine thereby
17368952	SOD1	SOD1	5.5	SOD1 mutation can disrupt the active-site pocket in the SOD1 dimer
17368952	SOD1	SOD1	5.5	SOD1 mutation can disrupt the active-site pocket in the SOD1 dimer to allow greater access of ONOO _amp_#x2212 to the
17368952	SOD1	SOD1	5.5	of ALS in the G93A transgenic mice compared with normal SOD1 mice and Nc mice ( Almer et al. 1999
17368952	SOD1	mSOD1	2.7	On the other hand a transgenic cell line expressing mSOD1 releases less ONOO _amp_#x2212 than those expressing normal SOD1 (
17368952	SOD1	SOD1	5.5	expressing mSOD1 releases less ONOO _amp_#x2212 than those expressing normal SOD1 ( Cookson et al. 2002 and pharmacological inhibition or genetic
17368952	SOD1	SOD1	5.5	SOD1 and NOS were colocalized at the foci of NF accumulation
17368952	SOD1	SOD1	5.5	correlation between nitration and oxidation of proteins and mutation of SOD1 in this disease the present study using the G93A transgenic
17368952	SOD1	mSOD1	2.7	brain regions particularly between motor and sensory cortex in the mSOD1 mice and controls
17368952	SOD1	SOD1	5.5	further support for the correlation between RNS and mutation of SOD1 in ALS
17368952	SOD1	mSOD1	2.7	(Bar Bar Harbor ME USA were used mice overexpressing the mSOD1 gene (G93A) G93A from humans with familial ALS B6SJL-TgN(SOD1-G93A)1Gur, B6SJL-TgN
17368952	SOD1	SOD1	5.5	familial ALS B6SJL-TgN(SOD1-G93A)1Gur, B6SJL-TgN SOD1-G93A 1Gur mice overexpressing normal human SOD1 gene B6SJL-TgN(SOD1)2Gur, B6SJL-TgN SOD1 2Gur and Nc mice (B6SJLF1) B6SJLF1
17368952	SOD1	SOD1	5.5	SOD1-G93A 1Gur mice overexpressing normal human SOD1 gene B6SJL-TgN(SOD1)2Gur, B6SJL-TgN SOD1 2Gur and Nc mice (B6SJLF1) B6SJLF1 without gene overexpression
17368952	SOD1	mSOD1	2.7	in brain tissues the onset of ALS symptoms of the mSOD1 mice that we used was delayed due to a small
17368952	SOD1	mSOD1	2.7	Therefore mSOD1 SOD1 and Nc mice were used at 6_amp_#x2013 6.5 months
17368952	SOD1	SOD1	5.5	Therefore mSOD1 SOD1 and Nc mice were used at 6_amp_#x2013 6.5 months of
17368952	SOD1	mSOD1	2.7	The mSOD1 mice used for the immunohistochemical staining of oxidized or nitrated
17368952	SOD1	mSOD1	2.7	by 4_amp_#x2013 5 months therefore 3 month_amp_#xb1 1 week old mSOD1 mice and age matched SOD1 and Nc mice were used
17368952	SOD1	SOD1	5.5	3 month_amp_#xb1 1 week old mSOD1 mice and age matched SOD1 and Nc mice were used while paralysis was developing in
17368952	SOD1	mSOD1	2.7	3-NY- and DNP-positive neurons were only observed in mSOD1 mice in the movement-related brain regions
17368952	SOD1	mSOD1	2.7	of double immunofluorescence-stained 3-NY- and DNP-positive neurons in cross-sections of mSOD1 SOD1 and Nc mice
17368952	SOD1	SOD1	5.5	double immunofluorescence-stained 3-NY- and DNP-positive neurons in cross-sections of mSOD1 SOD1 and Nc mice
17368952	SOD1	SOD1	5.5	There are no 3-NY-positive neurons in Nc (A) A and SOD1 (D) D mice but large neurons were 3-NY-positive in mSOD1
17368952	SOD1	mSOD1	2.7	SOD1 (D) D mice but large neurons were 3-NY-positive in mSOD1 mice (G, G red arrowhead
17368952	SOD1	mSOD1	2.7	This demonstrates that more 3-NY-positive neurons were present in the mSOD1 mice compared with the Nc (A) A and SOD1 (D)
17368952	SOD1	SOD1	5.5	the mSOD1 mice compared with the Nc (A) A and SOD1 (D) D mouse
17368952	SOD1	mSOD1	2.7	Similarly 3-NY-positive neurons appeared only in the mSOD1 mice (H) H in the motor cortex (B, B E
17368952	SOD1	mSOD1	2.7	motor cortex (B, B E and H and in the mSOD1 mice (I) I in the cortex of the cerebellum (C,
17368952	SOD1	SOD1	5.5	and I except a few 3-NY-positive neurons were observed in SOD1 mice (F) F
17368952	SOD1	mSOD1	2.7	the brain (J, J K and L red arrowhead of mSOD1 mice
17368952	SOD1	mSOD1	2.7	higher in motor cortex than in sensory cortex of the mSOD1 mice
17368952	SOD1	mSOD1	2.7	the motor cortex significantly more neurons were nitrated in the mSOD1 mice (48.8_amp_#xb1;5.6%, 48.8_amp_#xb1 5.6% S.D. than in the Nc (8.7_amp_#xb1;2.2,
17368952	SOD1	SOD1	5.5	S.D. than in the Nc (8.7_amp_#xb1;2.2, 8.7_amp_#xb1 2.2 S.D. and SOD1 (9.5_amp_#xb1;0.4, 9.5_amp_#xb1 0.4 S.D. mice ( P _amp_#x3c 0.001 Fig
17368952	SOD1	mSOD1	2.7	number of 3-NY-positive neurons was also significantly higher in the mSOD1 mice (19.6_amp_#xb1;3.3%, 19.6_amp_#xb1 3.3% S.D. than in Nc (9.3_amp_#xb1;3.7%, 9.3_amp_#xb1
17368952	SOD1	SOD1	5.5	3.3% S.D. than in Nc (9.3_amp_#xb1;3.7%, 9.3_amp_#xb1 3.7% S.D. and SOD1 (9.6_amp_#xb1;0.6%, 9.6_amp_#xb1 0.6% S.D. mice ( P =0.008 Fig 2
17368952	SOD1	SOD1	5.5	B but the number was not different between Nc and SOD1 mice in either region
17368952	SOD1	mSOD1	2.7	cortex was significantly higher than in the sensory cortex in mSOD1 mice ( P =0.002 Fig 2 C demonstrating that neurons
17368952	SOD1	mSOD1	2.7	to nitration than neurons in the sensory cortex in the mSOD1 mice or more ONOO _amp_#x2212 was produced in the motor
17368952	SOD1	mSOD1	2.7	oxidation in motor cortex than in sensory cortex of the mSOD1 mice
17368952	SOD1	SOD1	5.5	and only a few DNP-positive neurons (1.38_amp_#xb1;0.39) 1.38_amp_#xb1 0.39 in SOD1 mice significantly more DNP-positive neurons appeared in the motor cortex
17368952	SOD1	mSOD1	2.7	more DNP-positive neurons appeared in the motor cortex in the mSOD1 mice (31.3_amp_#xb1;9.5%, 31.3_amp_#xb1 9.5% S.D. than in the Nc and
17368952	SOD1	SOD1	5.5	mice (31.3_amp_#xb1;9.5%, 31.3_amp_#xb1 9.5% S.D. than in the Nc and SOD1 mice ( P =0.005 Fig 3 A
17368952	SOD1	SOD1	5.5	and only a few DNP-positive neurons (0.79_amp_#xb1;0.7) 0.79_amp_#xb1 0.7 in SOD1 mice while significantly more DNP-positive neurons (11.4_amp_#xb1;0.7%, 11.4_amp_#xb1 0.7% S.D.
17368952	SOD1	mSOD1	2.7	(11.4_amp_#xb1;0.7%, 11.4_amp_#xb1 0.7% S.D. appeared in the sensory cortex of mSOD1 mice than in the controls ( P _amp_#x3c 0.001 Fig
17368952	SOD1	mSOD1	2.7	the motor cortex than in the sensory cortex in the mSOD1 mice
17368952	SOD1	mSOD1	2.7	Protein-bound nitrotyrosine is significantly higher in mSOD1 mice than in controls as measured by HPLC
17368952	SOD1	mSOD1	2.7	We demonstrated that the levels of 3-NY in mSOD1 mice are significantly higher than in SOD1 mice ( P
17368952	SOD1	SOD1	5.5	of 3-NY in mSOD1 mice are significantly higher than in SOD1 mice ( P =0.00003 and Nc mice ( P =0.00005
17368952	SOD1	SOD1	5.5	and Nc mice ( P =0.00005 but not different between SOD1 and Nc mice ( P =0.4 Fig 4
17368952	SOD1	mSOD1	2.7	The level of 3-NY in mSOD1 mice is about 2.5-fold higher than its level in SOD1
17368952	SOD1	SOD1	5.5	mSOD1 mice is about 2.5-fold higher than its level in SOD1 and Nc mice
17368952	SOD1	SOD1	5.5	clearly correlates elevated protein nitration to the mutation of the SOD1 enzyme
17368952	SOD1	mSOD1	2.7	Significantly higher levels of _amp_#xb7 NO in mSOD1 mice than in the controls
17368952	SOD1	mSOD1	2.7	We found a significantly higher citrulline level in the mSOD1 mice than in the SOD1 mice ( P =0.02 and
17368952	SOD1	SOD1	5.5	higher citrulline level in the mSOD1 mice than in the SOD1 mice ( P =0.02 and Nc mice ( P =0.03
17368952	SOD1	mSOD1	2.7	The elevation of _amp_#xb7 NO in mSOD1 mice and the failure of normal SOD1 gene overexpressed in
17368952	SOD1	SOD1	5.5	_amp_#xb7 NO in mSOD1 mice and the failure of normal SOD1 gene overexpressed in the mouse to increase levels of _amp_#xb7
17368952	SOD1	mSOD1	2.7	work revealed that 3-NY- and DNP-positive neurons were observed in mSOD1 mice in all movement-related brain regions that we examined (the
17368952	SOD1	SOD1	5.5	This correlates mutation of SOD1 to nitration and oxidation of proteins in neurons in the
17368952	SOD1	mSOD1	2.7	the brain sections of both motor and sensory cortex in mSOD1 mice than in the corresponding regions of control mice (
17368952	SOD1	SOD1	5.5	A B further correlating nitration and oxidation of proteins to SOD1 mutation
17368952	SOD1	mSOD1	2.7	were significantly higher in both motor and sensory cortex in mSOD1 mice than in controls the motor cortex had significantly higher
17368952	SOD1	mSOD1	2.7	Fig 3 C neurons than did the sensory cortex in mSOD1 mice
17368952	SOD1	mSOD1	2.7	cortex than in neurons in the sensory cortex of the mSOD1 mice
17368952	SOD1	SOD1	5.5	Our comparisons strongly correlate mutation of SOD1 to nitration and oxidation of proteins in the movement brain
17368952	SOD1	mSOD1	2.7	3-NY were significantly ( 2.5-fold higher in the brains of mSOD1 mice than in controls ( Fig 4
17368952	SOD1	mSOD1	2.7	Figs 2 demonstrated significantly higher levels of protein nitration in mSOD1 mice compared with the controls
17368952	SOD1	SOD1	5.5	analysis ( Casoni et al. 2005 confirms the correlation between SOD1 mutation and protein nitration
17368952	SOD1	mSOD1	2.7	that the levels of _amp_#xb7 NO are significantly higher in mSOD1 transgenic mice than in their controls no difference was found
17368952	SOD1	SOD1	5.5	mice than in their controls no difference was found between SOD1 and Nc control groups ( Fig 5
17368952	SOD1	SOD1	5.5	NO is associated with ALS because overexpression of the normal SOD1 gene in the mouse did not increase levels of citrulline
17368952	SOD1	SOD1	5.5	et al. 1990 and in the extracellular fluid in G93A SOD1 mice ( Alexander et al. 2000 but the glutamate concentration
17368952	SOD1	mSOD1	2.7	that neither glutamate nor aspartate concentrations were significantly increased in mSOD1 mice compared with age-matched controls ( Fig 5 A consistent
17368952	SOD1	mSOD1	2.7	summary using double immunohistochemical staining of brain sections from the mSOD1 mice and the controls this work reveals that 1 3-NY-
17368952	SOD1	mSOD1	2.7	that 1 3-NY- and DNP-positive neurons were observed only in mSOD1 mice 2 nitration and oxidation of proteins were significantly higher
17368952	SOD1	mSOD1	2.7	nitration and oxidation of proteins were significantly higher in the mSOD1 mice than in the controls 3 the number of 3-NY-
17368952	SOD1	mSOD1	2.7	significantly higher in motor cortex than in sensory cortex in mSOD1 mice
17368952	SOD1	SOD1	5.5	These results correlate mutation of SOD1 to nitration and oxidation of proteins in neurons in the
17368952	SOD1	mSOD1	2.7	the motor cortex than of proteins in sensory cortex in mSOD1 mice
17368952	SOD1	mSOD1	2.7	the microdialysates and protein-bound nitrotyrosine in the brain tissue in mSOD1 SOD1 and Nc mice were measured
17368952	SOD1	SOD1	5.5	microdialysates and protein-bound nitrotyrosine in the brain tissue in mSOD1 SOD1 and Nc mice were measured
17368952	SOD1	mSOD1	2.7	both _amp_#xb7 NO and protein-bound 3-NY are significantly higher in mSOD1 mice than in control mice further supporting that RNS and
17496232	SOD	SOD	2.2	20-fold NO utilization in contrast addition of superoxide dismutase (SOD) SOD decreases NO utilization and prolongs its mean life and increases
17496232	SOD	SOD	2.2	At the same SOD level the production of ONOO (and and concurrent nitration at
17496232	SOD	SOD	2.2	Dismutation of O 2 by SOD proceeds with an order of magnitude lower than formation of
17496232	SOD1	SOD1	2.7	and 10-20% of cases are due to mutations in the SOD1 gene ( 122 123
17496232	SOD1	SOD1	2.7	Considering that SOD1 mutations lead to an increase of the denitrosylase activity of
17496232	SOD1	SOD1	2.7	increased denitrosylase activity is a toxic gain of function of SOD1 mutants
17584954	SOD1	Sod1	2.7	with muscle atrophy in aging in mice lacking CuZn-SOD ( Sod1 and in the neurodegenerative disease amyotrophic lateral sclerosis (ALS) ALS
17584954	SOD1	Sod1	2.7	In Sod1 mice muscle mitochondrial ROS production is increased >100% in 20-mo
17584954	SOD1	Sod1	2.7	is a knockout mouse lacking a major antioxidant enzyme CuZn-SOD Sod1 mice ( 67
17584954	SOD1	Sod1	2.7	In a recent study we reported that the Sod1 mice show a dramatic age-related loss of skeletal muscle mass
17584954	SOD1	Sod1	2.7	By 20 mo of age the Sod1 mice have lost nearly 50% of their hindlimb muscle mass
17584954	SOD1	Sod1	2.7	The Sod1 mice are also characterized by very high levels of oxidative
17584954	SOD1	Sod1	2.7	that occurs in the three conditions we studied (aging, aging Sod1 mice and ALS is largely the result of loss of
17584954	SOD1	Sod1	2.7	The Sod1 mice used in this study were generated by Dr Charles
17584954	SOD1	Sod1	2.7	The mice were maintained in the heterozygous state ( Sod1 and backcrossed with C57Bl/6J C57Bl 6J females (Jackson Jackson Laboratory
17584954	SOD1	Sod1	2.7	associated with significant loss of muscle mass age-related muscle atrophy Sod1 mice (a a mouse model of accelerated sarcopenia and two
17584954	SOD1	Sod1	2.7	of muscle atrophy is lowest higher in muscle from the Sod1 mice and increased nearly 10-fold in G93A ALS mutant mice
17584954	SOD1	Sod1	2.7	production and atrophy were higher in 20-mo-old than in 5-mo-old Sod1 mice and ROS generation was higher in the G93A compared
17584954	SOD1	Sod1	2.7	to denervation (caused caused by breakdown of neuromuscular junctions in Sod1 mice ( 25 57 70
17584954	SOD1	Sod1	2.7	Thus one common characteristic of the three models (aging, aging Sod1 mice and ALS mutant mice is alterations in innervation of
17584954	SOD1	Sod1	2.7	on our experiments in young and old wild-type mice the Sod1 model and the ALS mouse models we cannot be certain
17584954	SOD1	Sod1	2.7	generation precedes or follows changes in innervation especially in the Sod1 mice and in the case of aging in which the
17584954	SOD1	Sod1	2.7	2 O 2 release was in fact lower in old Sod1 and late-stage G93A ALS skeletal muscle mitochondria conditions that are
17584954	SOD1	Sod1	2.7	Increased ROS generation in skeletal muscle mitochondria from Sod1 mice
17584954	SOD1	Sod1	2.7	of gastrocnemius muscle isolated from female wild-type (WT) WT and Sod1 mice at 5 and 20 mo of age
17584954	SOD1	Sod1	2.7	substrate in isolated muscle mitochondria from 8 WT and 8 Sod1 mice at 20 mo of age * P _lt_ 0.05
17584954	SOD1	Sod1	2.7	open bars represent 5-mo-old WT light shaded bars represent 5-mo-old Sod1 dark shaded bars represent 20-mo-old WT and solid bars represent
17584954	SOD1	Sod1	2.7	shaded bars represent 20-mo-old WT and solid bars represent 20-mo-old Sod1
17584954	SOD1	Sod1	2.7	in mitochondria from 5-mo-old WT ( n = 21 and Sod1 mice ( n = 10 and 20-mo-old WT ( n
17584954	SOD1	Sod1	2.7	10 and 20-mo-old WT ( n = 16 and old Sod1 mice ( n = 16 values in D are means
17584954	SOD1	Sod1	2.7	in H 2 O 2 release in muscle mitochondria from Sod1 mice compared with mitochondria from age-matched WT mice (ANOVA ANOVA
17584954	SOD1	Sod1	2.7	Skeletal muscle mitochondrial ROS production is increased in Sod1 null mice and is associated with the degree of muscle
17584954	SOD1	Sod1	2.7	In agreement with our previous report on Sod1 mice ( 57 the gastrocnemius mass was significantly decreased in
17584954	SOD1	Sod1	2.7	both young (5 5 mo and older (20 20 mo Sod1 mice compared with the age-matched wild-type mice ( Fig 2
17584954	SOD1	Sod1	2.7	was decreased ~36% in mitochondria isolated from muscle of 20-mo-old Sod1 mice compared with mitochondria from muscle of age-matched wild-type mice
17584954	SOD1	Sod1	2.7	1 ROS production was increased over 30% in mitochondria from Sod1 mice at as early as 5 mo of age compared
17584954	SOD1	Sod1	2.7	By 20 mo of age ROS production in mitochondria from Sod1 mice was threefold higher than in the age-matched wild-type mice
17584954	SOD1	Sod1	2.7	2 _amp_#183 min _amp_#183 mg protein in mitochondria from 5-mo-old Sod1 compared with 19.77 _amp_#177 1.78 pmol H 2 O 2
17584954	SOD1	Sod1	2.7	In 20-mo-old Sod1 mice the increase in ROS generation with the substrates glutamate
17584954	SOD1	Sod1	2.7	the substrate succinate was significantly lower in mitochondria from the Sod1 mice compared with wild-type controls especially in mitochondria from the
17584954	SOD1	Sod1	2.7	compared with wild-type controls especially in mitochondria from the 20-mo-old Sod1 mice ( Fig 2 D
17584954	SOD1	Sod1	2.7	the G93A mutants and in the 20-mo-old (late late stage Sod1 mice
17584954	SOD1	Sod1	2.7	the mitochondria from wild-type mice much higher than in the Sod1 mice or in old wild-type mice which had relatively less
17584954	SOD1	Sod1	2.7	As we had observed in mitochondria from the Sod1 mice ROS production with succinate as a substrate was lower
17584954	SOD1	Sod1	2.7	an even greater decrease than had been observed in the Sod1 mice approaching levels close to that measured in state 1
17584954	SOD1	Sod1	2.7	muscle mitochondria isolated from young and old wild-type mice 20-mo-old Sod1 mice and the two ALS mouse models is illustrated in
17634371	SOD1	SOD1	1.7	amyotrophic lateral sclerosis (ALS)-linked ALS -linked superoxide dismutase 1 (SOD1 SOD1 mutation NGF induced apoptosis even in the absence of an
17634371	SOD1	SOD1	1.7	The increased susceptibility of SOD1 motor neurons to NGF was associated to decreased nuclear factor
17634371	SOD1	SOD1	1.7	of glutathione in nontransgenic motor neurons reproduced the effect of SOD1 expression increasing their sensitivity to NGF
17634371	SOD1	SOD1	1.7	This apoptotic pathway is facilitated by the expression of ALS-linked SOD1 mutations and critically modulated by Nrf2 activity
17634371	SOD1	SOD1	1.7	occurring in transgenic mice overexpressing mutant Cu-Zn superoxide dismutase (SOD1) SOD1 (Lowry Lowry et al. 2001b Copray et al. 2003 Kust
17634371	SOD1	SOD1	1.7	by p75 in motor neurons and the impact of ALS-linked SOD1 expression
17634371	SOD1	SOD1	1.7	Motor neurons overexpressing ALS-linked SOD1 mutation showed greater susceptibility to the p75 -activated apoptotic pathway
17634371	SOD1	SOD1	1.7	Transgenic SOD1 and nontransgenic motor neurons were prepared in the same way
17634371	SOD1	SOD1	1.7	Sprague Dawley SOD1 L26H rats were kindly provided by Dr David S Howland
17634371	SOD1	SOD1	1.7	As a control the expression of human SOD1 was determined in the spinal cord of E15 embryos and
17634371	SOD1	SOD1	1.7	Anti-SOD1 antibodies were developed in rabbit using recombinant pure human SOD1 as immunogen (kindly kindly provided by Dr M Marin University
17634371	SOD1	SOD1	1.7	Nontransgenic and SOD1 motor neuron cultures were maintained for 16 h in the
17634371	SOD1	SOD1	1.7	Moreover ALS-linked SOD1 overexpression increases motor neuron vulnerability to NGF-mediated apoptosis by reducing
17634371	SOD1	SOD1	1.7	effect could be explained not only by the expression of SOD1 with aberrant redox properties (Beckman Beckman et al. 2001 but
17634371	SOD1	SOD1	1.7	Interestingly the spinal cord of ALS patients and SOD1 mice exhibit a remarkable increase in ceramides and cholesterol esters
17634371	SOD1	SOD1	1.7	It was previously shown that motor neurons overexpressing ALS-linked SOD1 mutations (G37R, G37R G85R or G93A display increased susceptibility to
17634371	SOD1	SOD1	1.7	We show here that transgenic SOD1 motor neurons also show increased susceptibility to p75 -mediated apoptosis
17634371	SOD1	SOD1	1.7	In contrast to nontransgenic motor neurons SOD1 motor neurons are sensitive to NGF-mediated apoptosis in the absence
17634371	SOD1	SOD1	1.7	source of nitric oxide is not required NGF-induced apoptosis in SOD1 transgenic motor neurons requires endogenous production of nitric oxide by
17634371	SOD1	SOD1	1.7	the execution of a similar apoptotic pathway in nontransgenic and SOD1 motor neurons
17634371	SOD1	SOD1	1.7	The increased susceptibility of SOD1 motor neurons to NGF-induced apoptosis was not mediated by increased
17634371	SOD1	SOD1	1.7	The expression of mutant SOD1 leads to decreased antioxidant defenses thereby potentiating the detrimental stress
17634371	SOD1	SOD1	1.7	Compared with nontransgenic motor neurons SOD1 motor neurons showed reduced Nrf2 mRNA expression which correlated with
17634371	SOD1	SOD1	1.7	a motor neuron-like NSC34 cell line transfected with a mutant SOD1 expression vector and in motor neurons from SOD1-associated familial ALS
17634371	SOD1	SOD1-associated	1.7	a mutant SOD1 expression vector and in motor neurons from SOD1-associated familial ALS cases (Kirby Kirby et al. 2005
17634371	SOD1	SOD1	1.7	reduction in Nrf2 expression could explain the increased susceptibility of SOD1 motor neurons not only to NGF but also to Fas-mediated
17634371	SOD1	SOD1	1.7	prevented NGF- and Fas-mediated motor neuron apoptosis in nontransgenic and SOD1 motor neurons
17634371	SOD1	SOD1	1.7	Motor neurons overexpressing SOD1 show increase susceptibility to NGF-induced apoptosis
17634371	SOD1	SOD1	1.7	A Motor neurons isolated from SOD1 or nontransgenic (Non-Tg) Non-Tg E15 embryos were maintained in the
17634371	SOD1	SOD1	1.7	B SOD1 transgenic motor neurons were exposed to NGF in the presence
17634371	SOD1	SOD1	1.7	C Fluorescence microphotographs showing cytochrome c immunoreactivity in SOD1 motor neurons maintained with GDNF and exposed to vehicle (control)
17634371	SOD1	SOD1	1.7	the fluorescence emission of mito-HE ( exc 405 nm in SOD1 motor neurons immediately after NGF addition ( t = 0
17634371	SOD1	SOD1	1.7	E SOD1 transgenic motor neurons were exposed to NGF in the presence
17634371	SOD1	SOD1	1.7	F Western blot showing the expression of human mutant SOD1 (hSOD1) hSOD1 in the spinal cord and isolated motor neurons
17634371	SOD1	hSOD1	1.7	Western blot showing the expression of human mutant SOD1 (hSOD1) hSOD1 in the spinal cord and isolated motor neurons from transgenic
17634371	SOD1	SOD1	1.7	Only the endogenous rat SOD1 (rSOD1) rSOD1 was detected in either the spinal cord or
17634371	SOD1	SOD1	1.7	Reduced antioxidant defenses in SOD1 motor neurons
17634371	SOD1	SOD1	1.7	SOD1 and nontransgenic (Non-Tg) Non-Tg motor neuron cultures were maintained with
17634371	SOD1	SOD1	1.7	Increased Nrf2 activation prevents SOD1 motor neuron death induced by NGF or sFasL
17634371	SOD1	SOD1	1.7	A SOD1 motor neuron cultures maintained with GDNF (1 1 ng/ml) ng
17634371	SOD1	SOD1	1.7	B SOD1 or nontransgenic (Non-Tg) Non-Tg motor neuron cultures were maintained in
17634371	SOD1	SOD1	1.7	In contrast to nontransgenic motor neurons SOD1 -expressing motor neurons were sensitive to NGF-induced apoptosis in the
17634371	SOD1	SOD1	1.7	The expression of SOD1 in transgenic motor neurons under our culture conditions was confirmed
17634371	SOD1	SOD1	1.7	and found to be significantly higher than the endogenous rat SOD1
17634371	SOD1	SOD1	1.7	to NGF-induced apoptosis did not further decrease the survival of SOD1 -expressing motor neurons ( Fig 3 A
17634371	SOD1	SOD1	1.7	NGF-induced apoptosis in SOD1 -expressing motor neurons was prevented by blocking antibodies to p75
17634371	SOD1	SOD1	1.7	Moreover p75 -mediated apoptosis in SOD1 motor neurons was prevented by nSMase inhibitors ( Fig 3
17634371	SOD1	SOD1	1.7	mitoCP (1 1 n M also prevented NGF-induced apoptosis in SOD1 motor neurons ( Fig 3 E
17634371	SOD1	SOD1	1.7	of nitric oxide is not required for NGF to induce SOD1 motor neuron death N -nitro-L -arginine methyl ester (NAME) NAME
17634371	SOD1	SOD1	1.7	of the neuronal isoform of NOS prevented NGF-induced apoptosis in SOD1 motor neurons ( Fig 3 E
17634371	SOD1	SOD1	1.7	results indicate that the apoptotic pathway induced by NGF in SOD1 motor neurons required endogenous nitric oxide production by nNOS activation
17634371	SOD1	SOD1	1.7	The increased sensitivity of SOD1 motor neurons to NGF could not be explained by differential
17634371	SOD1	SOD1	1.7	in p75 and nNOS mRNA expression levels between nontransgenic and SOD1 motor neurons as determined by RT-PCR (data data not shown
17634371	SOD1	SOD1	1.7	the expression of the transcription factor Nrf2 was observed in SOD1 motor neurons compared with nontransgenic ones ( Fig 4
17634371	SOD1	SOD1	1.7	Nrf2 activation by tBHQ also prevented NGF-induced apoptosis in SOD1 motor neurons ( Fig 6 A
17634371	SOD1	SOD1	1.7	effect of tBHQ on apoptosis induced by Fas ligand in SOD1 -expressing motor neurons
17634371	SOD1	SOD1	1.7	Rat SOD1 motor neurons also displayed increased sensitivity to Fas-mediated apoptosis (
17634371	SOD1	SOD1	1.7	of motor neuron survival induced by sFasL was higher in SOD1 cultures than in nontransgenic reaching a plateau at concentrations >0.5
17719032	SOD1	SOD1	1.4	mutant forms of the enzyme Cu Zn superoxide dismutase (SOD1), SOD1 which are associated with familial ALS in humans
17719032	SOD1	SOD1	1.4	indicate that the rate of progression of MN loss in SOD1 mutant mice varies bidirectionally with the level of expression of
17719032	SOD1	SOD1	1.4	in a distinct form of familial ALS not linked to SOD1 ( Lai et al. 2006 and a Ca-AMPA channel blocker
17719032	SOD1	SOD1	1.4	Ca-AMPA channel blocker 1-naphthyl acetylspermine (NAS) NAS in G93A transgenic SOD1 rats
17719032	SOD1	SOD1	1.4	Male hemizygous SOD1 G93A transgenic rats [Tac:N:(SD)-TgN(SOD1G93A)L26H, Tac N SD -TgN SOD1G93A L26H
17719032	SOD1	SOD1	1.4	NAS slows MN loss in G93A SOD1 transgenic rats
17719032	SOD1	SOD1	1.4	As previously reported hemizygous G93A SOD1 transgenic rats generally develop symptoms between 115 and 130_amp_#xa0 days
17719032	SOD1	SOD1	1.4	Effects of NAS on glial pathology in G93A SOD1 transgenic rats
17719032	SOD1	SOD1	1.4	astrogliosis nitrotyrosine labeling and loss of astrocytic glutamate transport in SOD1 mutant rodent models of ALS ( Alexander et al. 2000
17719032	SOD1	SOD1	1.4	as MNs is well documented in both sporadic human and SOD1 linked forms of the disease ( Beal et al. 1997
17719032	SOD1	SOD1	1.4	Of note while SOD1 mutations only account for a small percentage of human ALS
17719032	SOD1	SOD1	1.4	between MNs and glia which we suggest are unique to SOD1 linked forms of disease transporter loss and oxidative tissue damage
17719032	SOD1	SOD1	1.4	It has become increasingly clear that MN degeneration in SOD1 linked models of ALS is non-cell-autonomous with the genotype of
17956327	SOD	SOD	0.9	SOD (superoxide superoxide dismutase prevent excessive ROS accumulation 46
17956327	SOD	SOD	0.9	AIH-induced pLTF also requires ROS since pre-treatment with a SOD mimetic abolishes pLTF 23
17956327	SOD	SOD	0.9	following AIH although changes in superoxide anion levels (e.g e.g SOD mimetic can disrupt levels of other ROS species such as
17956327	SOD	SOD	0.9	with okadaic acid restores pLTF in animals pre-treated with a SOD mimetic (P.M P.M MacFarlane and G.S Mitchell unpublished work but
17956327	SOD	SOD	0.9	kinase B PKC protein kinase C ROS reactive oxygen species SOD superoxide dismutase TrkB tropomyosin receptor kinase B
17987632	SOD1	SOD1	1.9	In AD and PD patients superoxide dismutase (SOD1) SOD1 was also indicated as a major target of oxidative damage
17987632	SOD1	SOD1	1.9	In particular in brain tissue of these patients different SOD1 isoforms have been identified although their functional role still remains
17987632	SOD1	SOD1	1.9	In the light of the possibility that different SOD1 entities could be expressed also in other neurodegenerative disorders as
17987632	SOD1	SOD1	1.9	sclerosis (ALS) ALS using human neuroblastoma SH-SY5Y cells with mutated SOD1 gene H46R as cellular model 2-DE using a narrow-range IPG
17987632	SOD1	SOD1	1.9	linear 15% SDS-PAGE in the second allowed to separate different SOD1 spots
17987632	SOD1	SOD1	1.9	This is the first report in which the presence of SOD1 (iso) iso forms in a cellular model of ALS has
18219386	SOD1	SOD1	2.5	Abstract Mutation in superoxide dismutase_amp_#x02013 1 (SOD1) SOD1 causes the inherited degenerative neurological disease familial amyotrophic lateral sclerosis
18219386	SOD1	SOD1	2.5	amyotrophic lateral sclerosis (ALS), ALS a non_amp_#x02013 cell-autonomous disease mutant SOD1 synthesis in motor neurons and microglia drives disease onset and
18219386	SOD1	SOD1	2.5	this issue of the JCI Harraz and colleagues demonstrate that SOD1 mutants expressed in human cell lines directly stimulate NADPH oxidase
18219386	SOD1	SOD1	2.5	lateral sclerosis Nox NADPH oxidase O 2 _amp_#x02022 _amp_#x02013 superoxide SOD1 superoxide dismutase_amp_#x02013 1
18219386	SOD1	SOD1	2.5	ROS by microglial Nox2 during inflammation is amplified by mutant SOD1 binding to Rac1 in ALS
18219386	SOD1	SOD1	2.5	cases of disease mutations in the superoxide dismutase_amp_#x02013 1 ( SOD1 gene are the most frequently identified
18219386	SOD1	SOD1	2.5	SOD1 catalyzes the conversion of superoxide (O2 O2 _amp_#x02022 _amp_#x02013 to
18219386	SOD1	SOD1	2.5	Indeed SOD1 mimetics have been reported to slow disease progression when administered
18219386	SOD1	SOD1	2.5	more compelling are data obtained by selective silencing of mutant SOD1 synthesis by microglia ( 11 or replacement of the mutant
18219386	SOD1	SOD1	2.5	Both approaches demonstrate that mutant SOD1 synthesis in inflammatory cells of the CNS directly accelerates the
18219386	SOD1	SOD1	2.5	By crossing mice expressing the SOD1 G93A mutant with mice lacking a catalytic subunit of Nox
18219386	SOD1	SOD1	2.5	progressive microglial activation during disease Nox2 expression was upregulated in SOD1 G93A mice ( 13 14 and sporadic ALS patients (
18219386	SOD1	SOD1	2.5	However in the case of ALS associated with SOD1 mutations the new data reported by Harraz Engelhardt and colleagues
18219386	SOD1	SOD1	2.5	( 20 provide a direct link between the disease-causing mutant SOD1 and Nox-mediated ROS production by microglial cells through SOD1 binding
18219386	SOD1	SOD1	2.5	mutant SOD1 and Nox-mediated ROS production by microglial cells through SOD1 binding to the Nox activator Rac1 thereby influencing the non_amp_#x02013
18219386	SOD1	SOD1	2.5	Mutant SOD1 stimulates Rac1-GTP activation of Nox and production of ROS
18219386	SOD1	SOD1	2.5	Rac1 from different mouse tissues Harraz and colleagues proposed that SOD1 interacts directly with Rac1 but not with the other Nox2
18219386	SOD1	SOD1-interacting	2.2	It is puzzling why multiple earlier screens for SOD1-interacting proteins including yeast 2-hybrid approaches did not identify Rac1
18219386	SOD1	SOD1	2.5	_amp_#x02013 that is converted to H 2 O 2 by SOD1 it was further tested whether the enzymatic activity of SOD1
18219386	SOD1	SOD1	2.5	SOD1 it was further tested whether the enzymatic activity of SOD1 was important for this interaction of SOD1 with Rac1
18219386	SOD1	SOD1	2.5	enzymatic activity of SOD1 was important for this interaction of SOD1 with Rac1
18219386	SOD1	SOD1	2.5	Only the metalated (native) native form of SOD1 bound to Rac1 while the demetalated (enzymatically enzymatically inactive SOD1
18219386	SOD1	SOD1	2.5	SOD1 bound to Rac1 while the demetalated (enzymatically enzymatically inactive SOD1 did not
18219386	SOD1	SOD1	2.5	In addition the binding of SOD1 to Rac1 was redox sensitive and could be cycled between
18219386	SOD1	SOD1	2.5	Under reducing conditions SOD1 efficiently bound Rac1-GTP the form of Rac1 that is recruited
18219386	SOD1	SOD1	2.5	The binding of SOD1 to Rac1-GTP inhibited the intrinsic and/or and or GAP-facilitated GTPase
18219386	SOD1	SOD1	2.5	It is now widely accepted that ALS-linked mutations in SOD1 provoke disease due to the acquisition of one or more
18219386	SOD1	SOD1	2.5	the acquisition of one or more toxic properties of mutant SOD1 ( 2
18219386	SOD1	SOD1	2.5	in tissues from mice expressing the catalytically active ALS-linked mutant SOD1 G93A but not in tissues from mice expressing comparably high
18219386	SOD1	SOD1	2.5	not in tissues from mice expressing comparably high levels of SOD1 WT (Figure Figure 1 and ref 20
18219386	SOD1	SOD1	2.5	also seen in glial and neuronal cell lines expressing mutant SOD1 G93A and SOD1 L8Q but not SOD1 WT and was
18219386	SOD1	SOD1	2.5	glial and neuronal cell lines expressing mutant SOD1 G93A and SOD1 L8Q but not SOD1 WT and was accompanied by increased
18219386	SOD1	SOD1	2.5	lines expressing mutant SOD1 G93A and SOD1 L8Q but not SOD1 WT and was accompanied by increased cell death
18219386	SOD1	SOD1	2.5	In addition liver tissues from SOD1 G93A mice _amp_#x02014 in which no altered pathology is normally
18219386	SOD1	SOD1	2.5	_amp_#x02022 _amp_#x02013 in agreement with a direct effect of mutant SOD1 on Nox activation rather than a consequence of increased inflammation
18219386	SOD1	SOD1	2.5	direct effect of increased ROS as a result of mutant SOD1 within microglial cells obviously could influence the survival of motor
18219386	SOD1	SOD1	2.5	demonstrations of slowed disease progression after reducing or eliminating mutant SOD1 synthesis within the myeloid lineage ( 11 12
18219386	SOD1	SOD1	2.5	between increased production of O 2 _amp_#x02022 _amp_#x02013 by mutant SOD1 and elevated Rac1-GTP levels was seen not just for SOD1
18219386	SOD1	SOD1	2.5	SOD1 and elevated Rac1-GTP levels was seen not just for SOD1 G93A but also for 2 additional ALS-linked SOD1 mutants SOD1
18219386	SOD1	SOD1	2.5	just for SOD1 G93A but also for 2 additional ALS-linked SOD1 mutants SOD1 L8Q and SOD1 G10V ( 20
18219386	SOD1	SOD1	2.5	SOD1 G93A but also for 2 additional ALS-linked SOD1 mutants SOD1 L8Q and SOD1 G10V ( 20
18219386	SOD1	SOD1	2.5	also for 2 additional ALS-linked SOD1 mutants SOD1 L8Q and SOD1 G10V ( 20
18219386	SOD1	SOD1	2.5	property of the more than 115 different mutations in the SOD1 gene known to cause ALS
18219386	SOD1	SOD1	2.5	is independent of dismutase activity with multiple mutants (including including SOD1 G85R SOD1 H46R and SOD1 G127X shown to be causative
18219386	SOD1	SOD1	2.5	of dismutase activity with multiple mutants (including including SOD1 G85R SOD1 H46R and SOD1 G127X shown to be causative for disease
18219386	SOD1	SOD1	2.5	with multiple mutants (including including SOD1 G85R SOD1 H46R and SOD1 G127X shown to be causative for disease in humans and
18219386	SOD1	SOD1	2.5	Similarly the failure of demetalated SOD1 WT to bind and activate Rac1-GTP would predict that removal
18219386	SOD1	SOD1	2.5	Rac1-GTP would predict that removal of the copper chaperone for SOD1 (CCS) CCS would substantially slow disease but this was not
18219386	SOD1	SOD1	2.5	Thus only if SOD1 mutants increase Nox2 activity independently of their metalated state could
18219386	SOD1	SOD1	2.5	be a feature common to the broader set of ALS-linked SOD1 mutants
18219386	SOD1	SOD1	2.5	The addition of apocynin to the drinking water of SOD1 G93A ALS mice beginning at 2 weeks of age increased
18219386	SOD1	SOD1	2.5	greater than _amp_#x02014 the deletion of the Nox2 gene in SOD1 G93A mice previously reported by the same group ( 14
18219386	SOD1	SOD1	2.5	a neuronal cell line when cells were transfected with mutant SOD1 ( 20 providing support that apocynin effectiveness may be acting
18219386	SOD1	SOD1	2.5	( 13 but it is still unknown whether patients with SOD1 mutations generate similar or greater increases in Nox2 activity or
18219386	SOD1	SOD1	2.5	in the progression of disease and whether apocynin affects mutant SOD1 expression
18219386	SOD1	SOD1	2.5	disease and might therefore be a direct consequence of mutant SOD1 expression in the infected tissues deprived of Nox activity rather
18219386	SOD1	SOD1	2.5	With this new finding that interaction of metalated SOD1 with Rac1 serves to activate Nox2 and that mutant forms
18219386	SOD1	SOD1	2.5	Rac1 serves to activate Nox2 and that mutant forms of SOD1 amplify production of ROS by locking Nox2 in its activated
18219386	SOD1	SOD1	2.5	new hypothesis for the gain of toxic function of mutant SOD1 ( 20
18219386	SOD1	SOD1	2.5	Indeed normal SOD1 function typically defined only by its dismutase activity is now
18219386	SOD1	SOD1	2.5	of these additional properties could be induced by mutations in SOD1 as one of the toxic contributors in ALS
18308427	SOD	SOD	1.7	Antioxidant defense enzymes superoxide dismutase (SOD), SOD catalase (CAT), CAT glutathione peroxidase (GSHPx), GSHPx glutathione reductase (GR)
18308427	SOD	SOD	1.7	These enzymes include superoxide dismutase (SOD) SOD (E.C E.C No 1.15.1.1 that remove O 2_amp_#x2212 by catalyzing
18308427	SOD	SOD	1.7	the correlation if any between the lipid peroxidation (LPO), LPO SOD CAT GSH GSHPx GR and G-6-PDH levels and the progression
18308427	SOD	SOD	1.7	SOD activity was estimated by the method of Nishikimi et al
18308427	SOD	SOD	1.7	However the activities of SOD and GSHPx were found to be insignificantly changed in comparison
18308427	SOD	SOD	1.7	elevated blood free radical levels did not induce the erythrocyte SOD and GSHPx enzyme activities in sporadic amyotrophic lateral sclerosis patients
8588576	superoxide dismutase	superoxide dismutase	1.0	superoxide dismutase|
8841988	superoxide dismutase	superoxide dismutase	1.0	decreased cytochrome c oxidase activity but unchanged superoxide dismutase and glutathione peroxidase activities in the spinal cords of patients with amyotrophic lateral sclerosis.
8841988	superoxide dismutase	superoxide dismutase	1.0	we measured the antioxidant actions of superoxide dismutase sod glutathione peroxidase gsh px and cytochrome c oxidase co of the human spinal cord in patients with als in comparison with those in control patients.
8899665	superoxide dismutase 1	superoxide dismutase 1	1.0	evidence against increased oxidative stress in fibroblasts from patients with non superoxide dismutase 1 mutant familial amyotrophic lateral sclerosis.
8899665	superoxide dismutase 1	superoxide dismutase 1	1.0	in parallel fibroblasts were examined for signs of abnormal oxidative stress by study of reactive oxygen species metabolism and concurrently leukocyte dna from the same patients was examined for superoxide dismutase 1 sod1 mutations.
9007410	superoxide dismutase	superoxide dismutase	1.0	superoxide dismutase and oxygen radical neurotoxicity.
9007410	superoxide dismutase	superoxide dismutase	1.0	cytosolic cu zn superoxide dismutase normally defends against damage by reactive oxygen species; however mutant forms of the enzyme might instead contribute to damage of motor neurons n some amyotrophic lateral sclerosis patients.
9007410	superoxide dismutase	superoxide dismutase	1.0	possible mechanisms of oxidative injury to neurons are discussed with reference to cytosolic cu zn superoxide dismutase mutations and other factors which might enhance oxygen radical toxicity.
9044305	superoxide dismutase	superoxide dismutase	1.0	oxidative stress caused by glycation of cu zn superoxide dismutase and its effects on intracellular components.
9044305	superoxide dismutase	superoxide dismutase	1.0	accumulating evidence supports the concept that decreases in cu zn superoxide dismutase sod activity causes apoptotic cell death in neuronal cells.
9092140	superoxide dismutase	superoxide dismutase	1.0	[amyotrophic lateral sclerosis and superoxide dismutase a review]
9092140	superoxide dismutase	superoxide dismutase	1.0	the recent observation that mutations in cytosolic cuzn superoxide dismutase cuzn sod are associated with amyotrophic lateral sclerosis als suggests that the disease arises from a perturbation of the homeostasis of free radicals resulting in neuronal degeneration by reactive
9092140	superoxide dismutase	superoxide dismutase	1.0	superoxide dismutase|
9462746	superoxide dismutase	superoxide dismutase	1.0	genetic inactivation of the mitochondrial form of superoxide dismutase in mice results in dilated cardiomyopathy hepatic lipid accumulation and early neonatal death.
9462746	superoxide dismutase	superoxide dismutase	1.0	we report that treatment with the superoxide dismutase sod mimetic manganese 5 10 15 20 tetrakis 4 benzoic acid porphyrin mntbap rescues these sod2tm1cje / mutant mice from this systemic pathology and dramatically prolongs their survival.
9620775	superoxide dismutase	superoxide dismutase	1.0	the association between mutations in the gene encoding the oxygen radical metabolizing enzyme cuzn superoxide dismutase sod1 and loss of motorneurons in the brain and spinal cord that occurs in the life shortening paralytic disease familial amyotrophic lateral sclerosis fals; ref 4 suggests that chronic and unrepaired
9633809	superoxide dismutase	superoxide dismutase	1.0	transgenic mice that highly over express a mutated human cuzn superoxide dismutase sod1 gene [gly93 >ala; tgn sod1 g93a g1h line] found in some patients with familial als fals have been shown to develop motor neuron disease that is characterized by motor neuron loss in the lumbar a
9745361	superoxide dismutase	superoxide dismutase	1.0	ies by rosen and colleagues [ 53 ] linked als to reactive oxygen species toxicity since they showed that 15_amp_#x2013;20% of fals patients carry mis sense mutations in the gene encoding cu 2+ /zn 2+ superoxide dismutase sod1 .
9745361	superoxide dismutase	superoxide dismutase	1.0	in amyotrophic lateral sclerosis peroxynitrite onoo _amp_#x2212; or other noxious ros can be formed as a result of altered function of mutant superoxide dismutase sod1 .
10077670	superoxide dismutase 1	superoxide dismutase 1	1.0	abstract it has been reported that expression of familial amyotrophic lateral sclerosis fals associated mutant cu/zn superoxide dismutase 1 sod induces apoptosis of neuronal cells in culture associated with an increase in reactive oxygen species.
10077670	superoxide dismutase 1	superoxide dismutase 1	1.0	als amyotrophic lateral sclerosis sod cu/zn superoxide dismutase 1 fals familial als cyp cyclophilin wt wild type ngf nerve growth factor adv adenovirus csa cyclosporin a nmda n methyl d aspartate mptp mitochondrial permeability transition pore
10077670	superoxide dismutase 1	superoxide dismutase 1	1.0	in 1993 mutations in cu/zn superoxide dismutase 1 sod were found to be associated with 20_amp_#x00025; of cases of familial als fals 1 .
10077670	superoxide dismutase	superoxide dismutase	1.0	superoxide dismutase|calcineurin|immunophilins|
10544701	superoxide dismutase	superoxide dismutase	1.0	lateral amyotrophic sclerosis: the discovery of a mutation in the copper zinc superoxide dismutase gene in patients with lateral amyotrophic sclerosis has made it possible to analyze the events leading to neuron death in transgenic mice.
10593879	superoxide dismutase	superoxide dismutase	1.0	tive oxygen species ros play a role in the pathogenesis of amyotrophic lateral sclerosis als a unique microdialysis or microcannula sampling technique was used in mice transfected with a mutant cu zn superoxide dismutase sod1 gene from humans with familial als mice transfected with the normal human sod1 gene and normal mice.
10593879	superoxide dismutase	superoxide dismutase	1.0	key words: mutation of cu zn superoxide dismutase gene _amp_#149; transgenic mouse _amp_#149; hydrogen peroxide _amp_#149; hydroxyl radical _amp_#149; superoxide anion
10593879	superoxide dismutase	superoxide dismutase	1.0	the finding of a single site mutation in the cu zn superoxide dismutase sod1 gene in familial als fals patients 2 3 linked this disease to free radicals 4 .
10593879	superoxide dismutase	superoxide dismutase	1.0	mutations of the sod1 gene reduce superoxide dismutase activity 2 3 8 9 10 11 ; this should elevate levels of o 2 .
10593879	superoxide dismutase	superoxide dismutase	1.0	the sod1 dimer may act in tandem as a superoxide dismutase and a peroxidase.
10643818	superoxide dismutase	superoxide dismutase	1.0	some cases of familial amyotrophic lateral sclerosis are characterized by mutations of copper_amp_#x2013;zinc superoxide dismutase.
10643818	superoxide dismutase	superoxide dismutase	1.0	this question arises particularly in view of the observation that superoxide dismutase activities in erythrocytes from patients may be reduced by 50% compared with healthy controls [ 27 ].
10643818	superoxide dismutase	superoxide dismutase	1.0	superoxide dismutase may act as a peroxidase [ 33 and 34 ] with mutated superoxide dismutase catalyzing substrate oxidation by hydrogen peroxide at a higher rate than wild type enzyme [ 35 ].
10671549	superoxide dismutase	superoxide dismutase	1.0	cells transfected with either wild type wt or mutant g93a cu zn superoxide dismutase cu zn sod produced comparable amounts of nitrite/nitrate but showed different degree of apoptosis.
10671549	superoxide dismutase	superoxide dismutase	1.0	the enzyme superoxide dismutase sod may play a fundamental role in modulating no toxicity since it acts as an antioxidant dismutating o 2 .
10671549	superoxide dismutase	superoxide dismutase	1.0	cu zn superoxide dismutase activity cells attached and detached were washed and collected by centrifugation.
10671549	superoxide dismutase	superoxide dismutase	1.0	the abbreviations used are: no nitric oxide; wt sh sy5y transfected with wild type cu zn sod; g93a sh sy5y transfected with mutant g93a cu zn sod; cu zn sod copper zinc superoxide dismutase; gsno s nitrosoglutathione; nono diethylamine nonoate; nor 4 3 [ _amp_#177; e ethyl 2' [ e hydroxyimino] 5 nitro 3 exenecarbamo yl]pyridine; dcf da 2' 7' dichlorodihydrofluorescein diacetate; ac devd
10742195	superoxide dismutase	superoxide dismutase	1.0	the most important recent contribution to understanding basic neuronal cu 2+ metabolism has been the elaboration of the copper chaperone of superoxide dismutase ccs .
10742195	superoxide dismutase	superoxide dismutase	1.0	recently ccs was reported to play an essential role in loading cu 2+ onto superoxide dismutase sod 1 under conditions of low cytosolic cu 2+ [ 8 ].
10899935	superoxide dismutase	superoxide dismutase	1.0	calcineurin activity is regulated both by redox compounds and by mutant familial amyotrophic lateral sclerosis superoxide dismutase.
10899935	superoxide dismutase	superoxide dismutase	1.0	evidence for the existence of a redox regulation of this enzyme has been also obtained by overexpression of wild type antioxidant cu zn superoxide dismutase sod1 that promotes cn activity and protects it from oxidative inactivation.
10930589	superoxide dismutase	superoxide dismutase	1.0	about 2% of als cases are associated with missense mutations in the gene for cytosolic cu zn superoxide dismutase sod1 cuznsod [ 1 and 2 ].
11050436	superoxide dismutase	superoxide dismutase	1.0	the transformation of this superoxide into hydrogen peroxide and under certain conditions then into hydroxyl radicals is important in diseases where respiratory chain function is abnormal or where superoxide dismutase function is altered as in amyotrophic lateral sclerosis.
11050436	superoxide dismutase	superoxide dismutase	1.0	the mutations seen in cuznsod in als patients are odd in that they do not destroy superoxide dismutase activity even though they sometimes affect enzyme stability [ 5 6 and 29 ].
11050436	superoxide dismutase	superoxide dismutase	1.0	in mammals increased life span by transgenic modulation of levels of superoxide dismutase has not been observed [ 42 and 43 ].
11050436	superoxide dismutase	superoxide dismutase	1.0	the superoxide is converted to hydrogen peroxide h 2 o 2 by superoxide dismutase.
11223912	superoxide dismutase	superoxide dismutase	1.0	mitochondrial uncouplers markedly blocked acute excitotoxicity and membrane permeable superoxide dismutase mimics attenuated acute excitotoxicity induced by glutamate and nmda but not by alpha amino 3 hydroxy 5 methylisoxazole 4 propionate ampa or kainate.
11513882	superoxide dismutase	superoxide dismutase	1.0	approximately 10% of all familial cases of amyotrophic lateral sclerosis fals are linked to mutations in the sod1 gene which encodes the copper/zinc superoxide dismutase cuznsod .
11513882	superoxide dismutase	superoxide dismutase	1.0	mutations in the sod1 gene which encodes the enzyme copper/zinc superoxide dismutase are associated with familial amyotrophic lateral sclerosis fals a fatal neurodegenerative disorder affecting spinal cord and brain motor neurons [ 1 ].
11513882	superoxide dismutase	superoxide dismutase	1.0	in order to address our hypothesis that calcineurin is one of the targets we investigated the ability of four different copper/zinc superoxide dismutase cuznsod proteins three mutant forms and the wild type wt enzyme to protect calcineurin from oxidative inactivation in vitro.
11513882	superoxide dismutase	superoxide dismutase	1.0	therefore calcineurin would be an ideal candidate for a proposed influence of superoxide dismutase mutations on signal transduction pathways leading to a mutant steady state finally resulting in neurodegeneration.
11679167	superoxide dismutase	superoxide dismutase	1.0	the association of heat shock and oxidative stress is further supported by the data revealing that the superoxide dismutase genes are upregulated by heat shock costa et al. 1997 .
11679167	superoxide dismutase	superoxide dismutase	1.0	in agreement s. cerevisiae mutants deficient in antioxidant defences such as catalase superoxide dismutase and cytochrome c peroxidase are sensitive to a lethal heat shock and the overexpression of genes encoding catalase and superoxide dismutase increase the resistance to the severe heat shock davidson e
11679167	superoxide dismutase	superoxide dismutase	1.0	and cytochrome c peroxidase are sensitive to a lethal heat shock and the overexpression of genes encoding catalase and superoxide dismutase increase the resistance to the severe heat shock davidson et al. 1996 .
11679167	superoxide dismutase	superoxide dismutase	1.0	the link between ethanol and oxidative stress was revealed by different experimental evidences such as the increase of the mitochondrial superoxide dismutase mnsod activity by ethanol the high ethanol sensitivity of s. cerevisiae cells deficient in mnsod costa and costa and the induction of ctt1 gene upon ethanol stress schuller et al. 1994 .
11679167	superoxide dismutase	superoxide dismutase	1.0	hap1p regulates the transcriptional activation of the antioxidant genes such as sod2 mitochondrial superoxide dismutase cta1 peroxisomal catalase ctt1 cytosolic catalase and ubi4 polyubiquitin .
11679167	superoxide dismutase	superoxide dismutase	1.0	the accumulation of oxidised proteins carbonyls and mixed disulphides and the increased production of reactive oxygen species concomitant with a depletion of antioxidant defences glutathione and superoxide dismutase seem to be key factors in ageing and cell death.
11679167	superoxide dismutase	superoxide dismutase	1.0	both oxidative stress see above and apoptosis including chromatin fragmentation dna strand breaks and plasma membrane inversion laun et al. 2001 ; v the life span of non dividing yeast cells lacking superoxide dismutase is extended by overexpressing the anti apoptotic protein bcl 2 longo et al. 1999 .
11701756	superoxide dismutase	superoxide dismutase	1.0	oxidative inactivation of calcineurin by cu zn superoxide dismutase g93a a mutant typical of familial amyotrophic lateral sclerosis.
11701756	superoxide dismutase	superoxide dismutase	1.0	in a recent work we have observed that calcineurin activity is depressed in two models for familial amyotrophic lateral sclerosis fals associated with mutations of the antioxidant enzyme cu zn superoxide dismutase sod1 namely in neuroblastoma cells expressing either sod1 mutant g93a or mutant h46r and in brain areas from g93a transgenic mice.
11796206	superoxide dismutase	superoxide dismutase	1.0	we previously characterized the enhanced peroxidative activity of the human familial als fals mutants of copper zinc superoxide dismutase cuznsod a4v and g93a in vitro.
11905995	superoxide dismutase	superoxide dismutase	1.0	mitochondrial dysfunction is an early event of motor neuron degeneration in transgenic mice overexpressing mutant superoxide dismutase sod 1 gene and mitochondrial abnormality is observed in human als patients.
12218958	superoxide dismutase	superoxide dismutase	1.0	superoxide dismutase applications and relevance to human diseases.
12218958	superoxide dismutase	superoxide dismutase	1.0	superoxide dismutase sod catalyzes the conversion of single electron reduced species of molecular oxygen to hydrogen peroxide and oxygen.
12218958	superoxide dismutase	superoxide dismutase	1.0	among these cu zn superoxide dismutase sod1 is widely distributed and comprises 90% of the total sod.
12368231	superoxide dismutase	superoxide dismutase	1.0	defective cu zn superoxide dismutase sod1 is responsible for some types of amyotrophic lateral sclerosis and ventral horn motor neurons vmn have been shown to die through a mitochondria dependent apoptotic pathway after chronic exposure
12437573	superoxide dismutase	superoxide dismutase	1.0	we have recently observed that calcineurin activity is depressed in human neuroblastoma cells expressing cu zn superoxide dismutase sod1 mutant g93a and in brain areas from g93a transgenic mice and that mutant g93a sod1 oxidatively inactivates calcineurin in vitro.
12614931	superoxide dismutase	superoxide dismutase	1.0	to oxidative injury because of its high level of polyunsaturated fatty acids as substrates for lipid peroxidation high rate of oxygen consumption and low or moderate levels of the antioxidant enzymes superoxide dismutase catalase and gpx compared with kidney or liver [ 1 ].
12618129	superoxide dismutase 1	superoxide dismutase 1	1.0	mitochondrial respiratory chain dysfunction was also found in transgenic mice expressing a mutant form of superoxide dismutase 1 associated with familial als [ 15 ].
12654515	superoxide dismutase	superoxide dismutase	1.0	the landmark discovery that mutations of the copper_amp_#x2013;zinc superoxide dismutase sod1 gene cause a portion of human familial als and that transgenic animal models expressing mutant sod1 mimic human als have contributed significantly to our understanding of human als [ 5 18 37 41
12663085	superoxide dismutase 1	superoxide dismutase 1	1.0	since mutations of the superoxide dismutase 1 sod 1 gene were first identified in 1993 it has been considered a possible cause of familial als fals [ 76 ].
12684448	superoxide dismutase 1	superoxide dismutase 1	1.0	although a small percentage 1 2% of cases have been linked to mutations in the enzyme superoxide dismutase 1 sod1 rosen et al. 1993 the vast majority 90 95% are sporadic.
12718737	superoxide dismutase	superoxide dismutase	1.0	oxidative stress in neurodegenerative diseases: therapeutic implications for superoxide dismutase mimetics.
12718737	superoxide dismutase	superoxide dismutase	1.0	antioxidant enzymes such as superoxide dismutase sod catalase and glutathione peroxidase gpx have demonstrated therapeutic efficacy in models of neurodegeneration.
12718737	superoxide dismutase	superoxide dismutase	1.0	most recently sod mimetics small molecules which mimic the activity of endogenous superoxide dismutase have come to the forefront of antioxidant therapeutics.
12753090	superoxide dismutase	superoxide dismutase	1.0	proteasome activation and nnos down regulation in neuroblastoma cells expressing a cu zn superoxide dismutase mutant involved in familial als.
12753090	superoxide dismutase	superoxide dismutase	1.0	we demonstrated that expression of the fully active g93a cu zn superoxide dismutase mutant in neuroblastoma cells is associated with an increased level of oxidatively modified proteins in terms of carbonylated residues.
12753090	superoxide dismutase	superoxide dismutase	1.0	the altered rate of proteolysis observed in g93a cells was specific for nnos as cu zn superoxide dismutase cu zn sod degradation by proteasome was influenced neither by its mutation nor by increased proteasome activity.
12893007	superoxide dismutase	superoxide dismutase	1.0	about 20% of the fals cases which are dominantly inherited are linked with mutation in the gene encoding the superoxide dismutase sod 1 protein [ rosen et al ] .
12901835	superoxide dismutase	superoxide dismutase	1.0	we report that the expression of mutant g93a copper/zinc superoxide dismutase sod1 associated with familial amyotrophic lateral sclerosis specifically causes a decrease in mtt reduction rate and atp levels and an increase in both cytosolic and mitochondrial reactive oxygen spe
12901835	superoxide dismutase	superoxide dismutase	1.0	in the early 1990s it has been demonstrated that about 20% of familial als fals patients possess point mutations in the gene coding for the antioxidant enzyme cu zn superoxide dismutase sod1 [ siddique et al 1991 deng et al 1993 and rosen et al 1993 ].
12909279	superoxide dismutase	superoxide dismutase	1.0	these include enzymatic activities superoxide dismutase catalase peroxidase and peroxiredoxin low molecular weight antioxidant species vitamin e ascorbate glutathione plus more complex forms of protection such as systems for metal transport and buffering
12909279	superoxide dismutase	superoxide dismutase	1.0	to the concept that oxidative stress plays a major role in als as in other neurodegenerative diseases is provided by the observation that mutations in the gene coding for the antioxidant enzyme cu zn superoxide dismutase sod1 have been reported in fals patients [ 21 and 80 ].
13678536	superoxide dismutase	superoxide dismutase	1.0	cross talk of nitric oxide oxygen radicals and superoxide dismutase regulates the energy metabolism and cell death and determines the fates of aerobic life.
13678536	superoxide dismutase	superoxide dismutase	1.0	because mitochondria are the major site of free radical generation they are highly enriched with enzymes such as mn type superoxide dismutase in matrix and antioxidants including gsh on both sides of inner membranes thus minimizing oxidative stress in and around this organelle.
13678536	superoxide dismutase	superoxide dismutase	1.0	the present work shows that cu/zn type superoxide dismutase which has been postulated for a long time to be a cytosolic enzyme also localizes bound to inner membranes of mitochondria thereby minimizing oxidative stress in and around this organelle while mitoc
14572730	superoxide dismutase	superoxide dismutase	1.0	neurons but may also involve altered function of non neural cells. _amp_#x201c;non cell autonomous_amp_#x201d; death of neurons is induced by the pro oxidant activity of a mutant form of copper/zinc superoxide dismutase sod 1 in patients with familial als which supports a crucial role of glia in the pathogenesis of als. 6 7 and 8 several findings indicate that neuroinflammatory processes mediate als pathogenesis and
14625013	superoxide dismutase	superoxide dismutase	1.0	transgenic mice overexpressing the human mutated form g93a of cu zn superoxide dismutase msod1 develop motor neuron degeneration resembling amyotrophic lateral sclerosis.
14625013	superoxide dismutase	superoxide dismutase	1.0	the exact etiology of the disease is unknown but mutations in the gene encoding cu zn superoxide dismutase sod1 are found in approximately 2% of als patients [ 12 ].
14648077	superoxide dismutase 1	superoxide dismutase 1	1.0	to protect themselves from these ross the cells have developed both an antioxidant system containing superoxide dismutase 1 sod1 and a redox system including peroxiredoxin2 prx2 thioredoxin peroxidase and glutathione peroxidase1 gpx1 : sod1 converts superoxide radicals into hydrogen peroxide h 2 o 2 and h 2 o 2 is then co
14648077	superoxide dismutase 1	superoxide dismutase 1	1.0	keywords peroxiredoxin 2 glutathione peroxidase 1 redox system superoxide dismutase 1 familial amyotrophic lateral sclerosis
14648077	superoxide dismutase	superoxide dismutase	1.0	for the first antioxidant enzyme group three isoforms of superoxide dismutase sod [ec 1.15.1.1] have been identified: sod1 sod2 and sod3 [ 9 ].
14648077	superoxide dismutase	superoxide dismutase	1.0	table 1 characteristics of five fals cases fals familial amyotrophic lateral sclerosis sod superoxide dismutase lbhi lewy body like hyaline inclusion 2 bp two base pair pci posterior column involvement type + detected nd not determined as asphyxia ih intraperitoneal hemorrhage rd respiratory distress pn pneumo
14648077	superoxide dismutase 1	superoxide dismutase 1	1.0	similar stainability and immunolocalization of sod1 gpx1 and prx2 in the lbhi are observed lbhi lewy body like hyaline inclusion fals familial amyotrophic lateral sclerosis sod1 superoxide dismutase 1 gpx1 glutathione peroxidase1 prx2 peroxiredoxin2 .
14648077	superoxide dismutase 1	superoxide dismutase 1	1.0	the precise intra inclusional immunolocalizations of these three proteins differ from each other in this lbhi lbhi lewy body like hyaline inclusion fals familial amyotrophic lateral sclerosis sod1 superoxide dismutase 1 gpx1 glutathione peroxidase1 prx2 peroxiredoxin2 .
14648077	superoxide dismutase 1	superoxide dismutase1	1.0	round and sausage like lbhis in the neuropil are positive for both sod1 and prx2 arrows sod1 superoxide dismutase1 lbhi lewy body like hyaline inclusion prx2 peroxiredoxin2 .
14648077	superoxide dismutase 1	superoxide dismutase1	1.0	round lbhis in the neuropil are positive for both sod1 and gpx1 arrows sod1 superoxide dismutase1 lbhi lewy body like hyaline inclusion gpx1 glutathione peroxidase1 .
14698606	superoxide dismutase 1	superoxide dismutase 1	1.0	most cases are sporadic although a subset 10% is familial with 20% of these being linked to mutations in the enzyme superoxide dismutase 1 sod1 .
15031734	superoxide dismutase	superoxide dismutase	1.0	in the ad brain the activity of the antioxidant proteins catalase superoxide dismutase sod glutathione peroxidase and glutathione reductase are increased in the hippocampus and amygdala 9 10 .
15031734	superoxide dismutase	superoxide dismutase	1.0	modifications to proteins result in the impairment of enzymes for example glutamine synthase superoxide dismutase whereas ros interactions with dna lead to mutations.
15031734	superoxide dismutase	superoxide dismutase	1.0	a beta amyloid beta; ros reactive oxygen species; sod superoxide dismutase.
15031734	superoxide dismutase	superoxide dismutase	1.0	the normal function of superoxide dismutase sod is to convert toxic superoxide radicals into h 2 o 2 that are subsequently inactivated by catalase.
15208263	superoxide dismutase	superoxide dismutase	1.0	mutations in the gene coding for the ubiquitous anti oxidant enzyme cu zn superoxide dismutase sod1 are associated with familial amyotrophic lateral sclerosis fals a fatal disease characterized by selective loss of motor neurons.
15266948	superoxide dismutase	superoxide dismutase	1.0	melatonin has been shown to either stimulate gene expression for the antioxidant enzymes superoxide dismutase catalase glutathione peroxidase glutathione reductase or to increase their activity.
15333927	superoxide dismutase	superoxide dismutase	1.0	structure of the cytosolic cu zn superoxide dismutase from schistosoma mansoni.
15333927	superoxide dismutase	superoxide dismutase	1.0	cu zn superoxide dismutase cu zn sod is an essential enzyme for protecting cells from the toxic effects of reactive oxygen species.
15333927	superoxide dismutase	superoxide dismutase	1.0	this is the first report of a crystal structure of a cu zn superoxide dismutase derived from a human parasite.
15812313	superoxide dismutase	superoxide dismutase	1.0	mutations in the copper_amp_#47;zinc superoxide dismutase sod1 gene are known to be responsible for familial amyotrophic lateral sclerosis.
15812313	superoxide dismutase	superoxide dismutase	1.0	the mutation in the copper_amp_#47;zinc superoxide dismutase sod1 gene is known to be associated with the familial als fals because of some undefined property of mutant sod1 protein _amp_#91; 1 _amp_#93;.
15850589	superoxide dismutase	superoxide dismutase	1.0	nitrocellulose membranes were probed with a polyclonal sheep anti human superoxide dismutase cu/zn antibody 1:1000; calbiochem emd biosciences inc la jolla ca usa .
15863242	superoxide dismutase 1	superoxide dismutase 1	1.0	cu/zn superoxide dismutase 1 sod1 encoded on chromosome 21 is a key enzyme in metabolism of oxygen free radicals and oxidative stress.
15863242	superoxide dismutase 1	superoxide dismutase 1	1.0	the human cu/zn superoxide dismutase 1 gene hsod1 was the first chromosome 21 gene to be characterised groner et al. 1985 and it was even shown earlier to be overexpressed at the protein level in down syndrome ds; trisomy 21 patients sine
15896810	superoxide dismutase	superoxide dismutase	1.0	s such as polyunsaturated fatty acids and catecholamines; b relatively low levels of antioxidants such as glutathione and vitamin e and antioxidant enzymes such as glutathione peroxidase catalase and superoxide dismutase ; c the endogenous generation of reactive oxygen free radicals via several specific reactions; d the elevated content of iron in specific areas of the human brain such as globus pallidus and substant
15896810	superoxide dismutase	superoxide dismutase	1.0	the rate of this reaction is three times faster than the rate of superoxide dismutase sod in catalyzing the dismutation of the superoxide anion to hydrogen peroxide.
15896810	superoxide dismutase	superoxide dismutase	1.0	arable to the controls and a significant increase of glutathione bound to haemoglobin in erythrocytes have been demonstrated in frda patients [128] also associated with a significant elevation in the superoxide dismutase/glutathione peroxidase activity ratio and with an 83% rise of glutathione transferase activity in the blood [129] .
15964487	superoxide dismutase	superoxide dismutase	1.0	also its administration in mice expressing a mutant superoxide dismutase sod1 g37r at late presymptomatic stage delayed the onset of motor neuron degeneration and muscle strength decline and increased the longevity of sod1 g37r mice kriz et al. 2002 .
16026864	superoxide dismutase 1	superoxide dismutase 1	1.0	als is sporadic in 90% of cases; the remaining 10% are of genetic origin with a subset being induced by mutations in the enzyme superoxide dismutase 1 sod1 .
16026864	superoxide dismutase 1	superoxide dismutase 1	1.0	als related disturbance of mitochondrial respiration by mutant superoxide dismutase 1 sod1 or hypoxia results in increased formation of reactive oxygen species ros 48 and 49 .
16043017	superoxide dismutase	superoxide dismutase	1.0	familial als cases accounting for 10_amp_#x2013;15% of all als disease are caused by a gain of function mutation in cu zn superoxide dismutase sod1 .
16043017	superoxide dismutase	superoxide dismutase	1.0	inherited als accounts for 10_amp_#x2013;15% of cases and among all of the familial als fals patients 20_amp_#x2013;30% of them are caused by a gain of function mutation in cu zn superoxide dismutase sod1 [3] and [4] .
16046141	superoxide dismutase	superoxide dismutase	1.0	als occurs both as a sporadic and as a familial dominantly inherited disease fals and about one fifth of fals patients have mutations in the gene coding for the enzyme cu zn superoxide dismutase sod1 rosen et al. 1993 . fals sod1 mutations cause the appearance of a pro oxidant pro apoptotic function in a typically anti oxidant anti apoptotic enzyme rabizadeh et al. 1995 wiedau pazos et al. 1
16050975	superoxide dismutase	superoxide dismutase	1.0	however remarkable mitochondrial abnormalities have also been identified in transgenic mouse models of familial als expressing mutant cu zn superoxide dismutase sod1 .
16050975	superoxide dismutase 1	superoxide dismutase 1	1.0	approximately 20% of fals cases are due to mutations in the gene encoding superoxide dismutase 1 sod1; cu zn dismutase; mim147450 rosen et al. 1993 .
16050975	superoxide dismutase 1	superoxide dismutase 1	1.0	superoxide dismutase 1|superoxide dismutase|
16188953	superoxide dismutase 1	superoxide dismutase 1	1.0	finally both compounds were tested in superoxide dismutase 1 g93a mice a model of familial amyotrophic lateral sclerosis.
16188953	superoxide dismutase 1	superoxide dismutase 1	1.0	twenty percent of familial als cases are caused by mutations in superoxide dismutase 1 sod1 which expressed in mice result in a phenotype resembling the pathology in patients.
16194581	superoxide dismutase	superoxide dismutase	1.0	moreover the brain is not particularly endowed with antioxidant defenses: it has a very low level of catalase activity and only moderate amounts of the endogenous antioxidant enzymes superoxide dismutase and glutathione peroxidase.
16227974	superoxide dismutase	superoxide dismutase	1.0	approximately 10% of cases are inherited and roughly a quarter of these inherited forms result from mutations in the cytosolic form of the antioxidant protein superoxide dismutase sod1 1 .
16681429	superoxide dismutase	superoxide dismutase	1.0	methods: we determined activity of the following ades: copper zinc superoxide dismutase cuzn sod catalase cat glutathione peroxidase gsh px and glutathione reductase gr in erythrocytes from sporadic als patients [sals /+ ] familial als patients with the leu144phe mutation in the sod1 ge
16877542	superoxide dismutase 1	superoxide dismutase 1	1.0	ros reactive oxygen species sod1 superoxide dismutase 1 igf1 insulin like growth factor 1
16877542	superoxide dismutase 1	superoxide dismutase 1	1.0	insights into its neurodegenerative mechanisms followed the discovery that dominant mutations in the gene for superoxide dismutase 1 sod1 cause familial als 2 3 .
17099894	superoxide dismutase 1	superoxide dismutase 1	1.0	motor neuron degeneration in amyotrophic lateral sclerosis mutant superoxide dismutase 1 transgenic mice: mechanisms of mitochondriopathy and cell death.
17099894	superoxide dismutase 1	superoxide dismutase 1	1.0	the mechanisms of human mutant superoxide dismutase 1 msod1 toxicity to motor neurons mns are unresolved.
17105868	superoxide dismutase	superoxide dismutase	1.0	oxidative stress in als seems to be attributable to multiple factors including mitochondrial dysfunction reduced glutathione peroxidase activity and point mutations in the cu zn superoxide dismutase sod1 gene the last of which are present in approximately 20% of familial als cases rosen et al. 1993 .
17105868	superoxide dismutase	superoxide dismutase	1.0	abbreviations: als amyotrophic lateral sclerosis; page paw grip endurance; mfr mitochondrial free radicals; div days in vitro; bso dl buthionine [ s r ] sulfoximine; sod superoxide dismutase; ldh lactate dehydrogenase; fadd fas associated death domain.
17150307	superoxide dismutase	superoxide dismutase	1.0	mutations of cu zn superoxide dismutase sod1 gene cause motor neuron degeneration and have linked to 2_amp_#x02013;5% of als cases rosen et al. 1994 ; rosen et al. 1993 .
17150307	superoxide dismutase	superoxide dismutase	1.0	etal bovine serum _amp_#x003b3; gcs _amp_#x003b3; glutamylcysteine synthetase gsh glutathione gssg oxidized glutathione mbm monobromobimane pfa paraformaldehyde ros reactive oxygen species sod1 cu zn superoxide dismutase tunel terminal deoxynucleotidyl transferase mediated nick end labeling
17174478	superoxide dismutase	superoxide dismutase	1.0	mutations in a superoxide dismutase which removes oxygen free radicals may cause the neurodegenerative disease amyotrophic lateral sclerosis.
17174478	superoxide dismutase	superoxide dismutase	1.0	keywords: amyotrophic lateral sclerosis ataxia telangiectasia like disorder werner syndrome xeroderma pigmentosum nitric oxide synthase superoxide dismutase
17174478	superoxide dismutase	superoxide dismutase	1.0	ide e i or nnos endothelial inducible or neuronal nitric oxide synthase nosox nos catalytic oxygenase module nosred nos reductase module nhej nonhomologous end joining ros reactive oxygen species sod superoxide dismutase ssbs single strand breaks tc ner transcription coupled nucleotide excision repair thm thumb domain ttd trichothiodystropy ws werner syndrome xp xeroderma pigmentosum
17174478	superoxide dismutase	superoxide dismutase	1.0	most of these free radicals are rapidly scavenged in the cell by the superoxide dismutase sod enzymes.
17174478	superoxide dismutase	superoxide dismutase	1.0	ros and copper zinc superoxide dismutase
17174478	superoxide dismutase 1	superoxide dismutase1	1.0	however mutations in the superoxide dismutase1 sod1 gene give rise to approximately 20% of fals cases deng et al. 1993 rosen et al. 1993 rakhit et al. 2002 while mutations in several other genes including als2 setx or vapb cause much rarer forms
17174478	superoxide dismutase	superoxide dismutase	1.0	sod1 encodes a cytosolic copper zinc superoxide dismutase cu zn sod which similar to the mitochondrial mnsod is responsible for the disproportionation of harmful superoxide radicals to hydrogen peroxide and oxygen fridovich 1986 .
17191135	superoxide dismutase	superoxide dismutase	1.0	mccord and fridovich first described superoxide dismutase implying a potential physiological role of superoxide [ 2 ] subsequently confirmed in numerous studies [ 3 ].
17191135	superoxide dismutase	superoxide dismutase	1.0	in defense against this the cell has developed a number of antioxidant defense systems including superoxide dismutase the peroxidases the glutathione redox cycle with its associated constitutive enzymes as well as glutathione itself.
17192933	superoxide dismutase 1	superoxide dismutase 1	1.0	correction of humoral derangements from mutant superoxide dismutase 1 spinal cord.
17368952	superoxide dismutase	superoxide dismutase	1.0	effort to study the role of reactive species in amyotrophic lateral sclerosis als the goal of this work is to explore the correlation between nitration and oxidation of proteins and mutation of cu zn superoxide dismutase sod1 in als.
17368952	superoxide dismutase	superoxide dismutase	1.0	transgenic mice overexpressing the mutant cu zn superoxide dismutase msod1 gene from humans with familial als wild type mice overexpressing the normal human sod1 gene and normal mice without gene overexpression were used.
17368952	superoxide dismutase	superoxide dismutase	1.0	the discovery of mutation of the cu zn superoxide dismutase sod1 gene in familial als patients deng et al 1993 and rosen et al 1993 was the first breakthrough in identifying causes of familial als.
17368952	superoxide dismutase	superoxide dismutase	1.0	to explore how mutant cu zn superoxide dismutase msod1 causes als a transgenic mouse model was established by introducing a human mutant gly 93_amp_#x2192;ala g93a of the sod1 gene into the mouse gurney et al. 1994 ; these transgenic mice developed
17368952	superoxide dismutase	superoxide dismutase	1.0	superoxide dismutase sod is a major antioxidative defense enzyme converting superoxide anion o 2 _amp_#xb7; _amp_#x2212; to hydrogen peroxide h 2 o 2 which is reduced to h 2 o by catalase and selenium dependent glutathio
17496232	superoxide dismutase 1	superoxide dismutase 1	1.0	on the contrary lack of no disrupts pathways like s nitrosylation or h 2 o 2 production and likewise is a gateway to disease in amyotrophic lateral sclerosis with superoxide dismutase 1 mutations or to cancer proliferation.
17496232	superoxide dismutase	superoxide dismutase	1.0	in agreement supplementation of submitochondrial particles with complex i or complex ii substrates increases by 10 to 20 fold no utilization; in contrast addition of superoxide dismutase sod decreases no utilization and prolongs its mean life and increases h 2 o 2 110 .
17584954	superoxide dismutase	superoxide dismutase	1.0	mitochondria; reactive oxygen species; amyotrophic lateral sclerosis; copper zinc superoxide dismutase
17634371	superoxide dismutase 1	superoxide dismutase 1	1.0	in motor neurons overexpressing the amyotrophic lateral sclerosis als linked superoxide dismutase 1 sod1 mutation ngf induced apoptosis even in the absence of an external source of no.
17634371	superoxide dismutase	superoxide dismutase	1.0	induction of p75 renders motor neurons vulnerable to ngf induced apoptosis. p75 has been implicated in motor neuron death occurring in transgenic mice overexpressing mutant cu zn superoxide dismutase sod1 lowry et al. 2001b ; copray et al. 2003 ; kust et al. 2003 ; turner et al. 2003a b or after axotomy ferri et al. 1998 ; wiese et al. 1999 ; lowry et al. 2001a .
17719032	superoxide dismutase	superoxide dismutase	1.0	currently the best animal models of als are provided by rodents harboring mutant forms of the enzyme cu zn superoxide dismutase sod1 which are associated with familial als in humans.
17956327	superoxide dismutase	superoxide dismutase	1.0	sod superoxide dismutase ] prevent excessive ros accumulation [ 46 ].
17956327	superoxide dismutase	superoxide dismutase	1.0	lar signal regulated kinase; 5 ht 5 hydroxytryptamine; ltf long term facilitation; pltf phrenic ltf; pka protein kinase a; pkb protein kinase b; pkc protein kinase c; ros reactive oxygen species; sod superoxide dismutase; trkb tropomyosin receptor kinase b.
17987632	superoxide dismutase	superoxide dismutase	1.0	optimizing separation efficiency of 2 de procedures for visualization of different superoxide dismutase forms in a cellular model of amyotrophic lateral sclerosis.
17987632	superoxide dismutase	superoxide dismutase	1.0	in ad and pd patients superoxide dismutase sod1 was also indicated as a major target of oxidative damage.
18270519	superoxide dismutase	superoxide dismutase	1.0	the nitroxide radical by itself is also an antioxidant and can be used as a superoxide dismutase mimic krishna et al 1996a .
18308427	superoxide dismutase	superoxide dismutase	1.0	antioxidant defense enzymes: superoxide dismutase sod catalase cat glutathione peroxidase gshpx glutathione reductase gr and glucose 6 phosphate dehydrogenase g 6 pdh in the erythrocytes are capable of detoxifying reactive oxygen species produced en
18308427	superoxide dismutase	superoxide dismutase	1.0	these enzymes include superoxide dismutase sod e.c no 1.15.1.1 that remove o 2_amp_#x2212; by catalyzing its dismutation one o 2_amp_#x2212; being reduced to h 2 o 2 and another oxidized to o 2 [fridovich 1989] [halliwell 2001] and [liochev a
18308427	superoxide dismutase	superoxide dismutase	1.0	superoxide dismutase