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PMID	17105868 ( )
Title	Concurrent administration of Neu2000 and lithium produces marked improvement of motor neuron survival, motor function, and mortality in a mouse model of amyotrophic lateral sclerosis.
Abstract	The Fas pathway and oxidative stress mediate neuronal death in stroke and may contribute to neurodegenerative disease. We tested the hypothesis that these two factors synergistically produce spinal motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Levels of reactive oxygen species were increased in motor neurons from ALS mice compared with wild-type mice at age 10 weeks, before symptom onset. The proapoptotic proteins Fas, Fas-associated death domain, caspase 8, and caspase 3 were also elevated. Oral administration of 2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)-benzoic acid (Neu2000), a potent antioxidant, blocked the increase in reactive oxygen species but only slightly reduced activation of proapoptotic proteins. Administration of lithium carbonate (Li(+)), a mood stabilizer that prevents apoptosis, blocked the apoptosis machinery without preventing oxidative stress. Neu2000 or Li(+) alone significantly enhanced survival time and motor function and together had an additive effect. These findings provide evidence that jointly targeting oxidative stress and Fas-mediated apoptosis can prevent neuronal loss and motor dysfunction in ALS. Korea 442-749.

NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.

Targets by SciMiner Summary

HUGO ID	Symbol	Target Name	#Occur	ActualStr
11920	FAS	Fas (TNF receptor superfamily, member 6)	32	Fas \| Fas-signaling \| Fas-associated \|
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	17	caspase 3 \|
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	13	caspase 8 \| caspase-8 \|
3573	FADD	Fas (TNFRSF6)-associated via death domain	12	FADD \|
990	BCL2	B-cell CLL/lymphoma 2	10	Bcl-2 \| bcl 2 \|
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	9	SOD1 \| SOD \| superoxide dismutase \|
8024	NTF4	neurotrophin 4	4	NT-4 \| nt 4/5 \| NT-4/5 \|
26515	COQ10A	coenzyme Q10 homolog A (S. cerevisiae)	2	coenzyme q10 a \| Q10 \|
727	ARTN	artemin	2	neurotrophic factor \|
8023	NTF3	neurotrophin 3	2	neurotrophin 3 \| NT-3 \|
1033	BDNF	brain-derived neurotrophic factor	2	brain derived neurotrophic factor \|
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	1	Akt-1 \|
19986	CYCS	cytochrome c, somatic	1	cytochrome c \|
5464	IGF1	insulin-like growth factor 1 (somatomedin C)	1	insulin like growth factor 1 \|
1511	CASP9	caspase 9, apoptosis-related cysteine peptidase	1	caspase 9 \|
21354	TICAM2	toll-like receptor adaptor molecule 2	1	cytoplasmic adaptor \|
15917	PLCB1	phospholipase C, beta 1 (phosphoinositide-specific)	1	phospholipase c \|
592	XIAP	X-linked inhibitor of apoptosis	1	XIAP \|
11936	FASLG	Fas ligand (TNF superfamily, member 6)	1	fas ligand \|
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	1	nadph oxidase \|
7808	NGF	nerve growth factor (beta polypeptide)	1	nerve growth factor \|
8975	PIK3CA	phosphoinositide-3-kinase, catalytic, alpha polypeptide	1	phosphatidylinositol 3 kinase \|

Targets by SciMiner Full list

HUGO ID	Symbol	Name	ActualStr	Score	FlankingText
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	The Fas pathway and oxidative stress mediate neuronal death in stroke and
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	The proapoptotic proteins Fas Fas-associated death domain caspase 8 and caspase 3 were also
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas-associated	2.1	The proapoptotic proteins Fas Fas-associated death domain caspase 8 and caspase 3 were also elevated
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.3	The ratio of apoptotic cell death genes Bax to Bcl-2 is increased at both the mRNA and protein level in
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.3	spinal cord mitochondria but not liver mitochondria and binds to Bcl-2 (Pasinelli Pasinelli et al. 2004
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.3	Altered expression and dysfunction of Bcl-2 may contribute to the activation of mitochondrial apoptosis machinery such
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.3	In support of this idea overexpression of Bcl-2 or the caspase inhibitory protein XIAP prolongs survival and improves
592	XIAP	X-linked inhibitor of apoptosis	XIAP	1.1	this idea overexpression of Bcl-2 or the caspase inhibitory protein XIAP prolongs survival and improves motor performance in ALS mice expressing
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	2.4	G93A transgenic mice carrying the G93A human SOD1 mutation were obtained from the Jackson Laboratory (Bar Bar Harbor
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	In experiments investigating oxidative stress and activation of the Fas pathway mice received Neu2000 (30 30 mg/kg/day), mg kg day
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	The following primary antibodies were used Fas FADD (BD BD Bioscience Franklin Lakes NJ cleaved caspase 3
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	1.4	The following primary antibodies were used Fas FADD (BD BD Bioscience Franklin Lakes NJ cleaved caspase 3 and
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	2.4	These mechanisms include mitochondrial dysfunction SOD1 mutations and activation of Ca -permeable ionotropic glutamate receptors which
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	2.4	and point mutations in the Cu Zn superoxide dismutase ( SOD1 gene the last of which are present in approximately 20%
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	2.4	Two findings in particular suggest a strong link between the SOD1 gene mutation and oxidative stress
26515	COQ10A	coenzyme Q10 homolog A (S. cerevisiae)	Q10	0.9	(transgenic transgenic ALS mice administration of antioxidants such as coenzyme Q10 a component of the mitochondrial respiratory chain and creatine an
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	2.4	This raises the possibility that the SOD1 mutation not only enhances oxidative stress in lumbar motor neurons
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	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
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.3	effect may be attributable to interaction of mutant SOD1 and Bcl-2 causing mitochondrial dysfunction and subsequently increased sensitivity to oxidative stress
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	We found that expression of Fas and FADD were increased selectively in the ventral motor neurons
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	1.4	We found that expression of Fas and FADD were increased selectively in the ventral motor neurons of G93A
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas-signaling	1.8	In motor neurons of ALS mice the Fas-signaling pathway remained activated after complete blockade of oxidative stress by
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	In support of this Li blocked activation of the Fas pathway during serum deprivation-induced apoptosis and attenuated motor neuron degeneration
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	and attenuated motor neuron degeneration as well as activation of Fas caspase 8 and caspase 3 in the spinal cords of
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	Akt-1	0.0	that result in activation of the serine/threonine serine threonine kinase Akt-1 and phospholipase C gamma (Chalecka-Franaszek Chalecka-Franaszek and Chuang 1999 ~0.425
8023	NTF3	neurotrophin 3	NT-3	1.3	neurotrophins nerve growth factor brain-derived neurotrophic factor neurotrophin 3 (NT-3), NT-3 and NT-4/5 NT-4 5 promote neuronal survival by preventing programmed
8024	NTF4	neurotrophin 4	NT-4/5	1.3	growth factor brain-derived neurotrophic factor neurotrophin 3 (NT-3), NT-3 and NT-4/5 NT-4 5 promote neuronal survival by preventing programmed cell death
8024	NTF4	neurotrophin 4	NT-4	1.3	factor brain-derived neurotrophic factor neurotrophin 3 (NT-3), NT-3 and NT-4/5 NT-4 5 promote neuronal survival by preventing programmed cell death or
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	conclusion the present study suggests that oxidative stress and the Fas death pathway constitute two separate routes of the motor neuron
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	The Fas pathway is slowly activated even in the blockade of oxidative
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	Thus targeting both oxidative stress and the Fas apoptosis pathway with concurrent treatment with Neu2000 and Li may
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	A Western blot analysis showing expression of Fas FADD and actin in lumbar segments from control or G93A
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	1.4	A Western blot analysis showing expression of Fas FADD and actin in lumbar segments from control or G93A transgenic
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	Levels of Fas (b) b and FADD (c) c were measured and scaled
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	1.4	Levels of Fas (b) b and FADD (c) c were measured and scaled to actin mean _amp_#177
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	1.4	Western blot analysis of FADD and Fas after immunoprecipitation with Fas antibody in the same
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	Western blot analysis of FADD and Fas after immunoprecipitation with Fas antibody in the same samples shown
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	Western blot analysis of FADD and Fas after immunoprecipitation with Fas antibody in the same samples shown above (d) d
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	(b) b at 12 weeks of age after immuno-labeling with Fas antibody
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	Note increased levels of Fas in the motor neurons (arrows) arrows from G93A mice
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase-8	3.0	C Western blot analysis showing expression of cleaved caspase-8 cleaved caspase-3 and actin in lumbar segments from control or
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	1.4	C Western blot analysis of FADD after immunoprecipitation (IP) IP with Fas antibody cleaved caspase 8
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	Western blot analysis of FADD after immunoprecipitation (IP) IP with Fas antibody cleaved caspase 8 cleaved caspase 3 and actin in
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	F Western blot analysis of Fas FADD cleaved caspase 8 cleaved caspase 3 and actin in
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	1.4	F Western blot analysis of Fas FADD cleaved caspase 8 cleaved caspase 3 and actin in lumbar
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	Fas- and Fas ligand-mediated apoptosis plays a role in neuronal loss in animal
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	We examined whether the Fas pathway would mediate apoptosis in ALS mice
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	Expression of Fas and its cytoplasmic adaptor protein FADD and Fas-FADD interaction were
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	1.4	Expression of Fas and its cytoplasmic adaptor protein FADD and Fas-FADD interaction were also increased in the lumbar spinal
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	Immunohistochemistry revealed that Fas expression was increased selectively in large spinal motor neurons of
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	These findings suggest that Fas FADD caspase 8 and caspase 3 are activated in spinal
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	1.4	These findings suggest that Fas FADD caspase 8 and caspase 3 are activated in spinal motor
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas-signaling	1.8	No activation of the Fas-signaling molecules in G93A mice was detectable at 16 weeks of
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	We also investigated whether serum deprivation would activate the Fas apoptosis pathway and whether this activation was sensitive to Li
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	1.4	Interaction of FADD with Fas cleaved caspase 8 and cleaved caspase 3 were
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	Interaction of FADD with Fas cleaved caspase 8 and cleaved caspase 3 were all increased
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	the diet slightly but statistically insignificantly attenuated the increase in Fas FADD and cleaved caspase 8 and caspase 3 in the
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	1.4	diet slightly but statistically insignificantly attenuated the increase in Fas FADD and cleaved caspase 8 and caspase 3 in the lumbar
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	noteworthy that daily administration of Li completely blocked activation of Fas and its downstream mediators in G93A mice
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.9	Neu2000 can block both oxidative stress and activation of the Fas apoptosis pathway induced in the spinal cords of G93A mice
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	1.9	DIV days in vitro BSO DL -buthionine- S R -sulfoximine SOD superoxide dismutase LDH lactate dehydrogenase FADD Fas-associated death domain
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	1.4	-buthionine- S R -sulfoximine SOD superoxide dismutase LDH lactate dehydrogenase FADD Fas-associated death domain
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas-associated	2.1	S R -sulfoximine SOD superoxide dismutase LDH lactate dehydrogenase FADD Fas-associated death domain
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	the proapoptotic proteins fas fas associated death domain caspase 8 and caspase 3 were also elevated.
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	the proapoptotic proteins fas fas associated death domain caspase 8 and caspase 3 were also elevated.
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	the ratio of apoptotic cell death genes bax to bcl 2 is increased at both the mrna and protein level in spinal motor neurons from patients with als and from sod1 g93a mice mu et al. 1996 ; vukosavic et al. 1999 .
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	mutant sod1 g93a has been observed to aggregate in spinal cord mitochondria but not liver mitochondria and binds to bcl 2 pasinelli et al. 2004 .
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	altered expression and dysfunction of bcl 2 may contribute to the activation of mitochondrial apoptosis machinery such as caspase 9 caspase 3 and cytochrome c in spinal motor neurons of als transgenic mice and humans with als guegan et al. 200
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	altered expression and dysfunction of bcl 2 may contribute to the activation of mitochondrial apoptosis machinery such as caspase 9 caspase 3 and cytochrome c in spinal motor neurons of als transgenic mice and humans with als guegan et al. 2001 ; inoue et al. 2003 .
1511	CASP9	caspase 9, apoptosis-related cysteine peptidase	caspase 9	1.0	altered expression and dysfunction of bcl 2 may contribute to the activation of mitochondrial apoptosis machinery such as caspase 9 caspase 3 and cytochrome c in spinal motor neurons of als transgenic mice and humans with als guegan et al. 2001 ; inoue et al. 2003 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	altered expression and dysfunction of bcl 2 may contribute to the activation of mitochondrial apoptosis machinery such as caspase 9 caspase 3 and cytochrome c in spinal motor neurons of als transgenic mice and humans with als guegan et al. 2001 ; inoue et al. 2003 .
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	in support of this idea overexpression of bcl 2 or the caspase inhibitory protein xiap prolongs survival and improves motor performance in als mice expressing the sod1 g93a mutation kostic et al. 1997 ; inoue et al. 2003 .
5464	IGF1	insulin-like growth factor 1 (somatomedin C)	insulin like growth factor 1	1.0	surprisingly insulin like growth factor 1 prevents neuronal cell apoptosis and protects spinal motor neurons in als mice ryu et al. 1999 ; kaspar et al. 2003 but markedly potentiates neuronal cell necrosis induced by hydroxyl radical or glut
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	ctions were then reacted overnight at 4degreec with the primary antibodies: mouse anti fas bd biosciences san jose ca anti nitrotyrosine 4 microg/ml; upstate biotechnology lake placid ny anti cleaved caspase 3 cell signaling technology danvers ma and anti neun.
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	the following primary antibodies were used: fas fadd bd bioscience franklin lakes nj cleaved caspase 3 and cleaved caspase 8 1 microg/ml; cell signaling technology .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	the following primary antibodies were used: fas fadd bd bioscience franklin lakes nj cleaved caspase 3 and cleaved caspase 8 1 microg/ml; cell signaling technology .
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	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 .
26515	COQ10A	coenzyme Q10 homolog A (S. cerevisiae)	coenzyme q10 a	1.0	second in transgenic mice expressing the sod1 g93a mutation transgenic als mice administration of antioxidants such as coenzyme q10 a component of the mitochondrial respiratory chain and creatine an inhibitor of the mitochondrial transition pore reduces free radical formation and increases life span and motor performance matthews e
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	the latter effect may be attributable to interaction of mutant sod1 and bcl 2 causing mitochondrial dysfunction and subsequently increased sensitivity to oxidative stress pasinelli et al. 2004 .
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	we found that expression of fas and fadd were increased selectively in the ventral motor neurons of g93a transgenic mice and that this led to activation of caspase 8 and caspase 3.
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	we found that expression of fas and fadd were increased selectively in the ventral motor neurons of g93a transgenic mice and that this led to activation of caspase 8 and caspase 3.
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	in support of this li blocked activation of the fas pathway during serum deprivation induced apoptosis and attenuated motor neuron degeneration as well as activation of fas caspase 8 and caspase 3 in the spinal cords of als mice.
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	in support of this li blocked activation of the fas pathway during serum deprivation induced apoptosis and attenuated motor neuron degeneration as well as activation of fas caspase 8 and caspase 3 in the spinal cords of als mice.
8975	PIK3CA	phosphoinositide-3-kinase, catalytic, alpha polypeptide	phosphatidylinositol 3 kinase	1.0	0 blocks free radical neurotoxicity in cortical cell cultures at a dose as low as 0.3 microm and completely blocks free radical production after focal cerebral gwag et al. 2006 beta and activation of phosphatidylinositol 3 kinase that result in activation of the serine/threonine kinase akt 1 and phospholipase c gamma chalecka franaszek and chuang 1999 ~0.425 _amp_#177; 0.05 meq/l in blood below the therapeutic range 0.6 1.5 m
15917	PLCB1	phospholipase C, beta 1 (phosphoinositide-specific)	phospholipase c	1.0	completely blocks free radical production after focal cerebral gwag et al. 2006 beta and activation of phosphatidylinositol 3 kinase that result in activation of the serine/threonine kinase akt 1 and phospholipase c gamma chalecka franaszek and chuang 1999 ~0.425 _amp_#177; 0.05 meq/l in blood below the therapeutic range 0.6 1.5 meq/l in blood for treatment of manic episodes and depression in humans ross and fra
727	ARTN	artemin	neurotrophic factor	1.0	long term treatment with li increases expression of brain derived neurotrophic factor in the hippocampus and neocortex which mediates the antiapoptotic action of li fukumoto et al. 2001 .
1033	BDNF	brain-derived neurotrophic factor	brain derived neurotrophic factor	1.0	long term treatment with li increases expression of brain derived neurotrophic factor in the hippocampus and neocortex which mediates the antiapoptotic action of li fukumoto et al. 2001 .
727	ARTN	artemin	neurotrophic factor	1.0	the neurotrophins nerve growth factor brain derived neurotrophic factor neurotrophin 3 nt 3 and nt 4/5 promote neuronal survival by preventing programmed cell death or apoptosis but they markedly enhance necrotic degeneration of neurons exposed to oxidative stress koh et
8023	NTF3	neurotrophin 3	neurotrophin 3	1.0	the neurotrophins nerve growth factor brain derived neurotrophic factor neurotrophin 3 nt 3 and nt 4/5 promote neuronal survival by preventing programmed cell death or apoptosis but they markedly enhance necrotic degeneration of neurons exposed to oxidative stress koh et al. 1995 ; won
7808	NGF	nerve growth factor (beta polypeptide)	nerve growth factor	1.0	the neurotrophins nerve growth factor brain derived neurotrophic factor neurotrophin 3 nt 3 and nt 4/5 promote neuronal survival by preventing programmed cell death or apoptosis but they markedly enhance necrotic degeneration of neurons
8024	NTF4	neurotrophin 4	nt 4/5	1.0	the neurotrophins nerve growth factor brain derived neurotrophic factor neurotrophin 3 nt 3 and nt 4/5 promote neuronal survival by preventing programmed cell death or apoptosis but they markedly enhance necrotic degeneration of neurons exposed to oxidative stress koh et al. 1995 ; won et al. 2000 .
8024	NTF4	neurotrophin 4	nt 4/5	1.0	the neurotrophins nerve growth factor brain derived neurotrophic factor neurotrophin 3 nt 3 and nt 4/5 promote neuronal survival by preventing programmed cell death or apoptosis but they markedly enhance necrotic degeneration of neurons exposed to oxidative stress koh et al. 1995 ; won et al. 2000 .
1033	BDNF	brain-derived neurotrophic factor	brain derived neurotrophic factor	1.0	the neurotrophins nerve growth factor brain derived neurotrophic factor neurotrophin 3 nt 3 and nt 4/5 promote neuronal survival by preventing programmed cell death or apoptosis but they markedly enhance necrotic degeneration of neurons exposed to oxidative stress koh et
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	nadph oxidase	1.0	neurotrophins can induce oxidative stress through up regulation of nadph oxidase leading to neuronal cell necrosis kim et al. 2002 kim et al. 2002 .
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	c western blot analysis showing expression of cleaved caspase 8 cleaved caspase 3 and actin in lumbar segments from control or g93a mice at ages indicated a .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	c western blot analysis showing expression of cleaved caspase 8 cleaved caspase 3 and actin in lumbar segments from control or g93a mice at ages indicated a .
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	levels of cleaved caspase 8 b and caspase 3 c were measured and scaled to actin mean _amp_#177; s.e.m.
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	levels of cleaved caspase 8 b and caspase 3 c were measured and scaled to actin mean _amp_#177; s.e.m.
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	d fluorescence photomicrographs of lumbar ventral sections from control a and g93a mice b at 12 weeks of age immunolabeled with an antibody for cleaved caspase 3.
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	note activation of caspase 3 in the motor neurons arrows from g93a mice.
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	c western blot analysis of fadd after immunoprecipitation ip with fas antibody cleaved caspase 8 cleaved caspase 3 and actin in neuron rich cortical cell cultures deprived of serum for 12 h alone or in the presence of 1 microm neu2000 or 5 mm li .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	c western blot analysis of fadd after immunoprecipitation ip with fas antibody cleaved caspase 8 cleaved caspase 3 and actin in neuron rich cortical cell cultures deprived of serum for 12 h alone or in the presence of 1 microm neu2000 or 5 mm li .
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	f western blot analysis of fas fadd cleaved caspase 8 cleaved caspase 3 and actin in lumbar segments from control and g93a transgenic mice treated with saline neu2000 30 mg/kg/days or li 200 mg/kg/days for 4 weeks starting from 8 weeks of age a .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	f western blot analysis of fas fadd cleaved caspase 8 cleaved caspase 3 and actin in lumbar segments from control and g93a transgenic mice treated with saline neu2000 30 mg/kg/days or li 200 mg/kg/days for 4 weeks starting from 8 weeks of age a .
11936	FASLG	Fas ligand (TNF superfamily, member 6)	fas ligand	1.0	fas and fas ligand mediated apoptosis plays a role in neuronal loss in animal models of stroke martin et al. 2001 beta amyloid neurotoxicity in cultured cortical neurons su et al. 2003 .
21354	TICAM2	toll-like receptor adaptor molecule 2	cytoplasmic adaptor	1.0	expression of fas and its cytoplasmic adaptor protein fadd and fas fadd interaction were also increased in the lumbar spinal cord of g93a transgenic mice at 12 weeks of age compared with control mice fig 2a .
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	increased expression of the apoptosis inducing signaling complex was followed by activation of caspase 8 and caspase 3 in the lumbar spinal cord fig 2c .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	increased expression of the apoptosis inducing signaling complex was followed by activation of caspase 8 and caspase 3 in the lumbar spinal cord fig 2c .
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	the active form of caspase 3 was observed in spinal motor neurons from g93a mice fig 2d .
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	these findings suggest that fas fadd caspase 8 and caspase 3 are activated in spinal motor neurons and mediate subsequent neuronal apoptosis in als mice.
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	these findings suggest that fas fadd caspase 8 and caspase 3 are activated in spinal motor neurons and mediate subsequent neuronal apoptosis in als mice.
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	interaction of fadd with fas cleaved caspase 8 and cleaved caspase 3 were all increased in neuron rich cortical cell cultures deprived of serum for 8 h and these changes were blocked by the addition of li but not neu2000 fig 3c .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	interaction of fadd with fas cleaved caspase 8 and cleaved caspase 3 were all increased in neuron rich cortical cell cultures deprived of serum for 8 h and these changes were blocked by the addition of li but not neu2000 fig 3c .
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	daily administration of neu2000 in the diet slightly but statistically insignificantly attenuated the increase in fas fadd and cleaved caspase 8 and caspase 3 in the lumbar spinal cords of g93a transgenic mice at 12 weeks of age fig 3f .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	daily administration of neu2000 in the diet slightly but statistically insignificantly attenuated the increase in fas fadd and cleaved caspase 8 and caspase 3 in the lumbar spinal cords of g93a transgenic mice at 12 weeks of age fig 3f .
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	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.