SciMiner Result Report Page

Document Information

PMID	15896810 ( )
Title	Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia.
Abstract	There is significant evidence that the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Friedreich's ataxia (FRDA), multiple sclerosis and amyotrophic lateral sclerosis, may involve the generation of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) associated with mitochondrial dysfunction. The mitochondrial genome may play an essential role in the pathogenesis of these diseases, and evidence for mitochondria being a site of damage in neurodegenerative disorders is based in part on observed decreases in the respiratory chain complex activities in Parkinson's, Alzheimer's, and Huntington's disease. Such defects in respiratory complex activities, possibly associated with oxidant/antioxidant imbalance, are thought to underlie defects in energy metabolism and induce cellular degeneration. The precise sequence of events in FRDA pathogenesis is uncertain. The impaired intramitochondrial metabolism with increased free iron levels and a defective mitochondrial respiratory chain, associated with increased free radical generation and oxidative damage, may be considered possible mechanisms that compromise cell viability. Recent evidence suggests that frataxin might detoxify ROS via activation of glutathione peroxidase and elevation of thiols, and in addition, that decreased expression of frataxin protein is associated with FRDA. Many approaches have been undertaken to understand FRDA, but the heterogeneity of the etiologic factors makes it difficult to define the clinically most important factor determining the onset and progression of the disease. However, increasing evidence indicates that factors such as oxidative stress and disturbed protein metabolism and their interaction in a vicious cycle are central to FRDA pathogenesis. Brains of FRDA patients undergo many changes, such as disruption of protein synthesis and degradation, classically associated with the heat shock response, which is one form of stress response. Heat shock proteins are proteins serving as molecular chaperones involved in the protection of cells from various forms of stress. In the central nervous system, heat shock protein (HSP) synthesis is induced not only after hyperthermia, but also following alterations in the intracellular redox environment. The major neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Huntington's disease (HD) and FRDA are all associated with the presence of abnormal proteins. Among the various HSPs, HSP32, also known as heme oxygenase I (HO-1), has received considerable attention, as it has been recently demonstrated that HO-1 induction, by generating the vasoactive molecule carbon monoxide and the potent antioxidant bilirubin, could represent a protective system potentially active against brain oxidative injury. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing the heat shock response. This may open up new perspectives in medicine, as molecules inducing this defense mechanism appear to be possible candidates for novel cytoprotective strategies. In particular, manipulation of endogenous cellular defense mechanisms, such as the heat shock response, through nutritional antioxidants, pharmacological compounds or gene transduction, may represent an innovative approach to therapeutic intervention in diseases causing tissue damage, such as neurodegeneration. Faculty of Medicine, University of Catania, Catania, Viale Andrea Doria 6, 95100 Catania, Italy. calabres@mbox.unict.it

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
3951	FXN	frataxin	79	friedreich ataxia \| FRDA \| frataxin \|
5232	HSPA1A	heat shock 70kDa protein 1A	50	HSPs \| HSP72 \| HSP \| hsp70 \| HSP70 \| Hsp70 \|
5013	HMOX1	heme oxygenase (decycling) 1	24	HO-1 \| heme oxygenase 1 \| ho 1 \|
7872	NOS1	nitric oxide synthase 1 (neuronal)	13	NOS \| nNOS \|
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	7	iNOS \| nitric oxide synthase \|
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	6	NFKB \| NFkB-independent \|
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	5	SOD \| superoxide dismutase \|
118	ACO2	aconitase 2, mitochondrial	4	aconitase \|
11180	SOD2	superoxide dismutase 2, mitochondrial	4	manganese superoxide dismutase \| MnSOD \|
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	3	APP \| amyloid \|
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	3	tumor necrosis factor \| TNF \|
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	3	GAPDH \| glyceraldehyde 3 phosphate dehydrogenase \|
990	BCL2	B-cell CLL/lymphoma 2	3	Bcl-2 \| bcl 2 \|
5244	HSPA9	heat shock 70kDa protein 9 (mortalin)	3	GRP75 \|
4235	GFAP	glial fibrillary acidic protein	2	glial fibrillary acidic protein \|
1516	CAT	catalase	2	catalase \|
5247	HSPB2	heat shock 27kDa protein 2	2	HSP27 \|
7876	NOS3	nitric oxide synthase 3 (endothelial cell)	2	eNOS \|
6886	MAPK9	mitogen-activated protein kinase 9	2	SAPK \| jun kinase \|
10417	RPS27A	ribosomal protein S27a	2	ubiquitin \|
5238	HSPA5	heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa)	2	GRP78 \|
4646	GTF2A1	general transcription factor IIA, 1, 19/37kDa	2	glucose regulated protein \|
5241	HSPA8	heat shock 70kDa protein 8	2	HSC70 \|
5261	HSPD1	heat shock 60kDa protein 1 (chaperonin)	2	HSP60 \|
6204	JUN	jun oncogene	2	AP-1 \| JUN \|
5014	HMOX2	heme oxygenase (decycling) 2	2	ho 2 \| HO-2 \|
5269	HSPE1	heat shock 10kDa protein 1 (chaperonin 10)	2	HSP10 \|
1546	SERPINH1	serpin peptidase inhibitor, clade H (heat shock protein 47), member 1, (collagen binding protein 1)	2	HSP47 \|
17937	CUZD1	CUB and zona pellucida-like domains 1	1	erg 1 \|
4341	GLUL	glutamate-ammonia ligase (glutamine synthetase)	1	glutamine synthetase \|
26515	COQ10A	coenzyme Q10 homolog A (S. cerevisiae)	1	Q10 \|
2898	DLD	dihydrolipoamide dehydrogenase	1	diaphorase \|
939	BAG3	BCL2-associated athanogene 3	1	bcl 2 binding protein \|
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	1	caspase 3 \|
19986	CYCS	cytochrome c, somatic	1	cytochrome c \|
7553	MYC	v-myc myelocytomatosis viral oncogene homolog (avian)	1	myc \|
5962	IL10	interleukin 10	1	interleukin 10 \|
6876	MAPK14	mitogen-activated protein kinase 14	1	p38-kinase \|
10451	RRM1	ribonucleotide reductase M1	1	ribonucleotide reductase \|
3768	FMN1	formin 1	1	FMN \|
6014	IL4	interleukin 4	1	interleukin 4 \|
3415	EPO	erythropoietin	1	erythropoietin \|
1991	CKB	creatine kinase, brain	1	creatine kinase \|
399	ALB	albumin	1	serum albumin \|
31395	COX8B	cytochrome c oxidase, subunit 8B pseudogene	1	cytochrome c oxidase \|
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	1	ap 1 \|
5991	IL1A	interleukin 1, alpha	1	interleukin 1 \|
25806	GSTCD	glutathione S-transferase, C-terminal domain containing	1	glutathione s transferase \|
11740	TF	transferrin	1	transferrin \|
4827	HBB	hemoglobin, beta	1	hemoglobin \|
4638	GSTP1	glutathione S-transferase pi	1	glutathione transferase \|
6001	IL2	interleukin 2	1	interleukin 2 \|
2244	COQ7	coenzyme Q7 homolog, ubiquinone (yeast)	1	coenzyme q \|
11920	FAS	Fas (TNF receptor superfamily, member 6)	1	apo 1 \|
4817	HARS2	histidyl-tRNA synthetase 2, mitochondrial (putative)	1	HO-3 \|

Targets by SciMiner Full list

HUGO ID	Symbol	Name	ActualStr	Score	FlankingText
3951	FXN	frataxin	FRDA	4.3	neurodegenerative diseases including Parkinson's disease Alzheimer's disease Friedreich's ataxia (FRDA), FRDA multiple sclerosis and amyotrophic lateral sclerosis may involve the generation
3951	FXN	frataxin	FRDA	4.3	The precise sequence of events in FRDA pathogenesis is uncertain
3951	FXN	frataxin	FRDA	4.3	addition that decreased expression of frataxin protein is associated with FRDA
3951	FXN	frataxin	FRDA	4.3	Many approaches have been undertaken to understand FRDA but the heterogeneity of the etiologic factors makes it difficult
3951	FXN	frataxin	FRDA	4.3	and their interaction in a vicious cycle are central to FRDA pathogenesis
3951	FXN	frataxin	FRDA	4.3	Brains of FRDA patients undergo many changes such as disruption of protein synthesis
5232	HSPA1A	heat shock 70kDa protein 1A	HSP	3.4	In the central nervous system heat shock protein (HSP) HSP synthesis is induced not only after hyperthermia but also following
3951	FXN	frataxin	FRDA	4.3	ALS multiple sclerosis (MS), MS Huntington's disease (HD) HD and FRDA are all associated with the presence of abnormal proteins
5232	HSPA1A	heat shock 70kDa protein 1A	HSPs	3.7	Among the various HSPs HSP32 also known as heme oxygenase I (HO-1), HO-1 has
5013	HMOX1	heme oxygenase (decycling) 1	HO-1	2.9	various HSPs HSP32 also known as heme oxygenase I (HO-1), HO-1 has received considerable attention as it has been recently demonstrated
5013	HMOX1	heme oxygenase (decycling) 1	HO-1	2.9	received considerable attention as it has been recently demonstrated that HO-1 induction by generating the vasoactive molecule carbon monoxide and the
3951	FXN	frataxin	FRDA	4.3	neurodegenerative diseases including Alzheimer's and Parkinson's diseases ALS MS and FRDA
6204	JUN	jun oncogene	AP-1	1.8	and/or and or DNA binding of numerous transcription factors including AP-1 fos jun myc erg-1 SAPK and NFkB 3
7553	MYC	v-myc myelocytomatosis viral oncogene homolog (avian)	myc	0.3	DNA binding of numerous transcription factors including AP-1 fos jun myc erg-1 SAPK and NFkB 3
6886	MAPK9	mitogen-activated protein kinase 9	SAPK	1.3	of numerous transcription factors including AP-1 fos jun myc erg-1 SAPK and NFkB 3
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NFkB	0.3	transcription factors including AP-1 fos jun myc erg-1 SAPK and NFkB 3
5232	HSPA1A	heat shock 70kDa protein 1A	HSP	3.4	the central nervous system (CNS), CNS heat shock protein (HSP) HSP synthesis is induced not only after hyperthermia but also following
5232	HSPA1A	heat shock 70kDa protein 1A	HSP	3.4	is harmful and can lead to cell death induction of HSP synthesis can result in stress tolerance and cytoprotection in a
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.0	as increased expression of heat shock proteins antioxidant enzymes and Bcl-2 may be triggered to withstand all the above mentioned pathogenic
3951	FXN	frataxin	FRDA	4.3	may play an essential role in neurodegenerative diseases such as FRDA 9
3951	FXN	frataxin	FRDA	4.3	The precise sequence of events in FRDA pathogenesis is uncertain
3951	FXN	frataxin	FRDA	4.3	addition that decreased expression of frataxin protein is associated with FRDA 11
3951	FXN	frataxin	FRDA	4.3	the oxidative stress hypothesis which may underlie the pathogenesis of FRDA
3951	FXN	frataxin	FRDA	4.3	FRDA is an autosomal recessive degenerative disorder characterized by progressive gait
3951	FXN	frataxin	FRDA	4.3	Neuropathology in FRDA is characterized by early degeneration of large sensory neurons in
3951	FXN	frataxin	FRDA	4.3	Hypertrophic cardiomyopathy is present in large proportion FRDA patients 12 and 13
3951	FXN	frataxin	FRDA	4.3	The causative mutation of FRDA is an abnormally expanded GAA triplet repeat in the first
3951	FXN	frataxin	FRDA	4.3	expanded GAA triplet repeat in the first intron of the FRDA gene on chromosome 9q13 14
3951	FXN	frataxin	FRDA	4.3	Ninety-eight percent of FRDA patients are homozygous for the GAA expansion the remainder carrying
3951	FXN	frataxin	FRDA	4.3	GAA expansion the remainder carrying a repeat expansion in one FRDA allele and a point mutation in the other 12 and
3951	FXN	frataxin	FRDA	4.3	The size of the GAA expansion in FRDA patients ranges from about 100 repeats to 1700 12 and
3951	FXN	frataxin	FRDA	4.3	The expression of a number of symptoms/signs symptoms signs in FRDA is dependent upon the length of the GAA repeat expansion
3951	FXN	frataxin	FRDA	4.3	Mutations in the FRDA gene either GAA expansions or point mutations result in reduced
3951	FXN	frataxin	FRDA	4.3	In normal subjects the highest level of expression of the FRDA gene has been found in the heart and spinal cord
3951	FXN	frataxin	FRDA	4.3	The amount of residual frataxin in lymphoblastoid cell lines from FRDA patients correlates with the GAA expansion size in the smaller
118	ACO2	aconitase 2, mitochondrial	aconitase	1.6	mitochondrial respiratory chain complexes I and II/III II III and aconitase activities have been demonstrated in post-mortem cardiac muscle samples from
3951	FXN	frataxin	FRDA	4.3	been demonstrated in post-mortem cardiac muscle samples from patients with FRDA associated with reduced levels of mitochondrial DNA and with increased
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	Up-regulation of protein manganese superoxide dismutase (MnSOD) MnSOD fails to occur in FRDA fibroblasts exposed to iron 25
3951	FXN	frataxin	FRDA	4.3	protein manganese superoxide dismutase (MnSOD) MnSOD fails to occur in FRDA fibroblasts exposed to iron 25
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NFkB	0.3	with the observation of absent activation of the redox-sensitive factor NFkB suggest that a NFkB-independent pathway that may not require free
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NFkB-independent	0.3	absent activation of the redox-sensitive factor NFkB suggest that a NFkB-independent pathway that may not require free radical signaling is responsible
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	free radical signaling is responsible for the reduced induction of MnSOD 26
3951	FXN	frataxin	FRDA	4.3	Cardiac and skeletal muscle bioenergetics was investigated directly in FRDA patients using in vivo 31 P-MRS 41
3951	FXN	frataxin	FRDA	4.3	Cardiac bioenergetics was assessed in vivo in FRDA patients with and without left ventricular hypertrophy 43
3951	FXN	frataxin	FRDA	4.3	Cardiac PCr to ATP ratios in the FRDA group as a whole were reduced by about 40%
3951	FXN	frataxin	FRDA	4.3	were significantly reduced compared to controls in both groups of FRDA patients with normal and hypertrophic heart 43
3951	FXN	frataxin	FRDA	4.3	In FRDA the hypertrophic process may be compensatory and caused or contributed
3951	FXN	frataxin	FRDA	4.3	have shown a reduced rate of mitochondrial ATP synthesis in FRDA patients 46 and 47
3951	FXN	frataxin	FRDA	4.3	Mitochondrial V max for ATP production in FRDA patients was also significantly lower than in a group of
3951	FXN	frataxin	FRDA	4.3	se did not account for the reduced mitochondrial function in FRDA patients
3951	FXN	frataxin	FRDA	4.3	utilization of oxygen in response to exercise showed in several FRDA patients features related to inadequate oxygen utilization by muscle 48
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	Accordingly as cytokines promote the induction of NOS in brain a possible role for a glial-derived NO_amp_#xb7 in
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	study in which NADPH diaphorase (a a cytochemical marker of NOS activity positive glial cells have been identified in the substantia
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	2.7	this it has been reported that the selective inhibition of nNOS prevents 1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine (MPTP)-induced MPTP -induced Parkinsonism in
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	Role of NOS and NO in brain pathophysiology
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	responsible for NO synthesis is the nitric oxide synthase (NOS) NOS family of enzymes which catalyse the conversion of arginine to
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	NOS localized in the CNS and in the periphery 91 is
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	is present in three well characterized isoforms (a) a neuronal NOS (nNOS, nNOS type I (b) b endothelial NOS (eNOS; eNOS
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	2.7	in three well characterized isoforms (a) a neuronal NOS (nNOS, nNOS type I (b) b endothelial NOS (eNOS; eNOS type III
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	a neuronal NOS (nNOS, nNOS type I (b) b endothelial NOS (eNOS; eNOS type III and (c) c inducible NOS (iNOS,
7876	NOS3	nitric oxide synthase 3 (endothelial cell)	eNOS	2.2	NOS (nNOS, nNOS type I (b) b endothelial NOS (eNOS; eNOS type III and (c) c inducible NOS (iNOS, iNOS type
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	endothelial NOS (eNOS; eNOS type III and (c) c inducible NOS (iNOS, iNOS type II
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	2.7	(eNOS; eNOS type III and (c) c inducible NOS (iNOS, iNOS type II
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	Activation of different isoforms of NOS requires various factors and co-factors
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	complexes is a prerequisite before the functional active dimer exhibits NOS activity which depends also on cofactors such as tetrahydrobiopterin (BH
3768	FMN1	formin 1	FMN	0.2	also on cofactors such as tetrahydrobiopterin (BH BH 4 FAD FMN and NADPH 92
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	2.7	In contrast to nNOS and eNOS iNOS can bind to calmodulin even at very
7876	NOS3	nitric oxide synthase 3 (endothelial cell)	eNOS	2.2	In contrast to nNOS and eNOS iNOS can bind to calmodulin even at very low concentration
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	2.7	In contrast to nNOS and eNOS iNOS can bind to calmodulin even at very low concentration of
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	2.7	calmodulin even at very low concentration of intracellular calcium thus iNOS can exert its activity in a calcium-independent manner
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	2.7	The levels of iNOS in the CNS are generally fairly low
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	2.7	However an increased expression of iNOS in astrocytes and microglia occurs following viral infection and trauma
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	2.7	Activation of iNOS requires gene transcription and the induction can be influenced by
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	1.4	three times faster than the rate of superoxide dismutase (SOD) SOD in catalyzing the dismutation of the superoxide anion to hydrogen
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	1.4	Therefore when present at appropriate concentrations NO effectively competes with SOD for O 2 _amp_#x2212
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	GAPDH	1.6	demonstrated to stimulate the auto-ADP ribosylation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) GAPDH by reacting with a critical cysteine with resulting binding of
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	GAPDH	1.6	resulting binding of NAD to the catalytic cysteine inhibition of GAPDH activity and depression of glycolysis 104
4827	HBB	hemoglobin, beta	hemoglobin	1.0	Other heme protein targets for NO are catalase cytochrome c hemoglobin and peroxidase
118	ACO2	aconitase 2, mitochondrial	aconitase	1.6	sulfur cluster present in numerous enzymes including NADH-ubiquinone oxidoreductase cis -aconitase and NADH succinate oxidoreductase 108
118	ACO2	aconitase 2, mitochondrial	aconitase	1.6	iron metabolism at the post-transcriptional level by interacting with cytosolic aconitase which after binding NO functions as iron responsive binding protein
118	ACO2	aconitase 2, mitochondrial	aconitase	1.6	binding NO functions as iron responsive binding protein diminishing its aconitase activity 109
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.0	Accordingly the recent finding that _amp_#x3b2 -amyloid fragment 25_amp_#x2013 35 selectively decreases complex IV activity in isolated
3951	FXN	frataxin	FRDA	4.3	glutathione bound to haemoglobin in erythrocytes have been demonstrated in FRDA patients 128 also associated with a significant elevation in the
5232	HSPA1A	heat shock 70kDa protein 1A	HSP	3.4	In mammalian cells HSP synthesis is induced not only after hyperthermia but also following
5232	HSPA1A	heat shock 70kDa protein 1A	HSP	3.4	is harmful and can lead to cell death induction of HSP synthesis can result in stress tolerance and cytoprotection against stress-induced
5232	HSPA1A	heat shock 70kDa protein 1A	HSPs	3.7	Some of the known HSPs include ubiquitin HSP10 HSP27 HSP32 (or or HO-1 HSP47 HSP60
5269	HSPE1	heat shock 10kDa protein 1 (chaperonin 10)	HSP10	1.9	Some of the known HSPs include ubiquitin HSP10 HSP27 HSP32 (or or HO-1 HSP47 HSP60 HSC70 HSP70 (or
5247	HSPB2	heat shock 27kDa protein 2	HSP27	1.9	Some of the known HSPs include ubiquitin HSP10 HSP27 HSP32 (or or HO-1 HSP47 HSP60 HSC70 HSP70 (or or
5013	HMOX1	heme oxygenase (decycling) 1	HO-1	2.9	the known HSPs include ubiquitin HSP10 HSP27 HSP32 (or or HO-1 HSP47 HSP60 HSC70 HSP70 (or or HSP72 HSP90 and HSP100/105
1546	SERPINH1	serpin peptidase inhibitor, clade H (heat shock protein 47), member 1, (collagen binding protein 1)	HSP47	1.3	known HSPs include ubiquitin HSP10 HSP27 HSP32 (or or HO-1 HSP47 HSP60 HSC70 HSP70 (or or HSP72 HSP90 and HSP100/105 HSP100
5261	HSPD1	heat shock 60kDa protein 1 (chaperonin)	HSP60	1.9	HSPs include ubiquitin HSP10 HSP27 HSP32 (or or HO-1 HSP47 HSP60 HSC70 HSP70 (or or HSP72 HSP90 and HSP100/105 HSP100 105
5241	HSPA8	heat shock 70kDa protein 8	HSC70	1.9	include ubiquitin HSP10 HSP27 HSP32 (or or HO-1 HSP47 HSP60 HSC70 HSP70 (or or HSP72 HSP90 and HSP100/105 HSP100 105
5232	HSPA1A	heat shock 70kDa protein 1A	HSP70	5.5	ubiquitin HSP10 HSP27 HSP32 (or or HO-1 HSP47 HSP60 HSC70 HSP70 (or or HSP72 HSP90 and HSP100/105 HSP100 105
5232	HSPA1A	heat shock 70kDa protein 1A	HSP72	3.4	HSP32 (or or HO-1 HSP47 HSP60 HSC70 HSP70 (or or HSP72 HSP90 and HSP100/105 HSP100 105
5232	HSPA1A	heat shock 70kDa protein 1A	HSP70	5.5	HSP70
5241	HSPA8	heat shock 70kDa protein 8	HSC70	1.9	Included in this family are HSC70 (heat heat shock cognate the constitutive form HSP70 (the the
5232	HSPA1A	heat shock 70kDa protein 1A	HSP70	5.5	family are HSC70 (heat heat shock cognate the constitutive form HSP70 (the the inducible form also referred to as HSP72 GRP75
5232	HSPA1A	heat shock 70kDa protein 1A	HSP72	3.4	form HSP70 (the the inducible form also referred to as HSP72 GRP75 (a a constitutively expressed glucose-regulated protein found in the
5244	HSPA9	heat shock 70kDa protein 9 (mortalin)	GRP75	2.2	HSP70 (the the inducible form also referred to as HSP72 GRP75 (a a constitutively expressed glucose-regulated protein found in the endoplasmic
5232	HSPA1A	heat shock 70kDa protein 1A	HSP70	5.5	After a variety of central nervous system (CNS) CNS insults HSP70 is synthesized at high levels and is present in the
5232	HSPA1A	heat shock 70kDa protein 1A	HSPs	3.7	shock factors (HSFs) HSFs within the cytosol by dissociating other HSPs that are normally bound to HSF 132
5232	HSPA1A	heat shock 70kDa protein 1A	HSPs	3.7	different heat shock genes leading to transcription and synthesis of HSPs
5232	HSPA1A	heat shock 70kDa protein 1A	HSP70	5.5	After heat shock for instance the synthesis of HSP70 increases to a point to where it becomes the most
5232	HSPA1A	heat shock 70kDa protein 1A	HSP70	5.5	Once synthesized HSP70 binds to denaturated proteins in an ATP-dependent manner
5232	HSPA1A	heat shock 70kDa protein 1A	HSPs	3.7	In the nervous system HSPs are induced in a variety of pathological conditions including cerebral
5232	HSPA1A	heat shock 70kDa protein 1A	HSPs	3.7	Expression of the gene encoding HSPs has been found in various cell populations within the nervous
5232	HSPA1A	heat shock 70kDa protein 1A	HSPs	3.7	HSPs consist of both stress-inducible and constitutive family members
5232	HSPA1A	heat shock 70kDa protein 1A	HSP70	5.5	gene transfer has become possible to overexpress the gene encoding HSP70 to test directly the hypothesis that stress proteins protects cells
5232	HSPA1A	heat shock 70kDa protein 1A	HSP70	5.5	from injury and it has been demonstrated that overproduction of HSP70 leads to protection in several different models of nervous system
5232	HSPA1A	heat shock 70kDa protein 1A	HSP70	5.5	Following focal cerebral ischemia mRNA encoding HSP70 is synthesized in most ischemic cells except in areas of
5232	HSPA1A	heat shock 70kDa protein 1A	HSP70	5.5	HSP70 proteins is produced mainly in endothelial cells in the core
5232	HSPA1A	heat shock 70kDa protein 1A	HSP70	5.5	It has been suggested that this neuronal expression of HSP70 outside an infarct can be used to define the ischemic
5232	HSPA1A	heat shock 70kDa protein 1A	HSP	3.4	of in vitro studies show that both heat shock and HSP overproduction protect CNS cells against both necrosis and apoptosis
5232	HSPA1A	heat shock 70kDa protein 1A	HSP70	5.5	Transfection of cultured astrocytes with HSP70 protects them from ischemia or glucose deprivation 140
5232	HSPA1A	heat shock 70kDa protein 1A	HSP70	5.5	HSP70 has been demonstrated to inhibit caspase-3 activation caused by ceramide
6204	JUN	jun oncogene	JUN	1.8	to inhibit caspase-3 activation caused by ceramide and also affect JUN kinase and p38-kinase activation 141
6876	MAPK14	mitogen-activated protein kinase 14	p38-kinase	0.3	activation caused by ceramide and also affect JUN kinase and p38-kinase activation 141
5232	HSPA1A	heat shock 70kDa protein 1A	HSP70	5.5	In addition HSP70 binds to and modulates the function of BAG-1 the bcl-2
5232	HSPA1A	heat shock 70kDa protein 1A	HSP	3.4	between mechanisms of oxidative and/or and or nitrosative stress and HSP induction 143
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NFkB	0.3	shock response can exert its protective effects through inhibition of NFkB signaling pathway 132
5232	HSPA1A	heat shock 70kDa protein 1A	Hsp70	5.5	cytokine-induced nitrosative stress is associated with an increased synthesis of Hsp70 stress proteins
5232	HSPA1A	heat shock 70kDa protein 1A	Hsp70	5.5	Increase in Hsp70 protein expression was also found after treatment of cells with
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	5.5	(SNP), SNP thus suggesting a role for NO in inducing hsp70 proteins
5232	HSPA1A	heat shock 70kDa protein 1A	HSPs	3.7	Ubiquitin is one of the smallest HSPs and is expressed throughout brain in response to ischemia
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NFKB	0.3	targeting and chaperoning of proteins degraded in proteasomes which include NFKB cyclins HSFs hypoxia-inducible factor some apoptosis-related proteins tumor necrosis factor
5247	HSPB2	heat shock 27kDa protein 2	HSP27	1.9	HSP27 is synthesized mainly in astrocytes in response to ischemic situations
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF	1.2	It also protects against Fas-Apo-1 staurosporine TNF and etoposside-induced apoptotic cell death as well as H 2
1546	SERPINH1	serpin peptidase inhibitor, clade H (heat shock protein 47), member 1, (collagen binding protein 1)	HSP47	1.3	HSP47 is synthesized mainly in microglia following cerebral ischemia and subarachnoid
5261	HSPD1	heat shock 60kDa protein 1 (chaperonin)	HSP60	1.9	HSP60 glucose-regulated protein 75 (GRP75) GRP75 and HSP10 chaperone proteins within
5244	HSPA9	heat shock 70kDa protein 9 (mortalin)	GRP75	2.2	HSP60 glucose-regulated protein 75 (GRP75) GRP75 and HSP10 chaperone proteins within mitochondria
5269	HSPE1	heat shock 10kDa protein 1 (chaperonin 10)	HSP10	1.9	HSP60 glucose-regulated protein 75 (GRP75) GRP75 and HSP10 chaperone proteins within mitochondria
5244	HSPA9	heat shock 70kDa protein 9 (mortalin)	GRP75	2.2	GRP75 and GRP78 also called oxygen-regulated proteins (ORPs) ORPs are produced
5238	HSPA5	heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa)	GRP78	1.9	GRP75 and GRP78 also called oxygen-regulated proteins (ORPs) ORPs are produced
5238	HSPA5	heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa)	GRP78	1.9	GRP75 and GRP78 also called oxygen-regulated proteins (ORPs) ORPs are produced by low
5013	HMOX1	heme oxygenase (decycling) 1	HO-1	2.9	There are three isoforms of heme oxygenase HO-1 or inducible isoform HO-2 or constitutive isoform and the recently
5014	HMOX2	heme oxygenase (decycling) 2	HO-2	1.9	are three isoforms of heme oxygenase HO-1 or inducible isoform HO-2 or constitutive isoform and the recently discovered HO-3 149 150
4817	HARS2	histidyl-tRNA synthetase 2, mitochondrial (putative)	HO-3	0.3	inducible isoform HO-2 or constitutive isoform and the recently discovered HO-3 149 150 151 152 153 and 154
5013	HMOX1	heme oxygenase (decycling) 1	HO-1	2.9	The iron released by HO-1 is bound by ferritin perhaps via a HO-1 chaperone function
5013	HMOX1	heme oxygenase (decycling) 1	HO-1	2.9	released by HO-1 is bound by ferritin perhaps via a HO-1 chaperone function 155
5013	HMOX1	heme oxygenase (decycling) 1	HO-1	2.9	Increasing evidence suggests that the HO-1 gene is redox regulated and contains in its promoter region
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.0	of heat shock proteins is closely related to that of amyloid precursor protein (APP), APP heat-shock proteins have been studied in
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	APP	0.3	is closely related to that of amyloid precursor protein (APP), APP heat-shock proteins have been studied in brains of patients with
5013	HMOX1	heme oxygenase (decycling) 1	HO-1	2.9	Significant increases in the levels of HO-1 have been observed in AD brains in association with neurofibrillary
5013	HMOX1	heme oxygenase (decycling) 1	HO-1	2.9	in AD brains in association with neurofibrillary tangles 157 and HO-1 mRNA was found to be increased in AD neocortex and
5013	HMOX1	heme oxygenase (decycling) 1	HO-1	2.9	HO-1 increase was not only in association with neurofibrillary tangles but
5013	HMOX1	heme oxygenase (decycling) 1	HO-1	2.9	It is conceivable that the dramatic increase in HO-1 in AD may be a direct response to increased free
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NFkB	0.3	cell line it has recently been shown that curcumin inhibits NFkB activation effectively preventing neuronal cell death 159
5013	HMOX1	heme oxygenase (decycling) 1	HO-1	2.9	evidence has demonstrated that curcumin is a potent inducer of HO-1 in vascular endothelial cells 7 and 167
5013	HMOX1	heme oxygenase (decycling) 1	HO-1	2.9	(CAPE), CAPE an active component of propolis as a novel HO-1 inducer 162
3951	FXN	frataxin	FRDA	4.3	Therapy advances in FRDA
3951	FXN	frataxin	FRDA	4.3	The precise sequence of events in FRDA pathogenesis is uncertain
3951	FXN	frataxin	FRDA	4.3	FRDA offers a unique opportunity to intervene with _amp_#x201c neuroprotective_amp_#x201d therapy
3951	FXN	frataxin	FRDA	4.3	in the presence of advanced disease and established pathogenetic mechanisms FRDA patients can be diagnosed by genetic analysis either presymptomatically or
3951	FXN	frataxin	FRDA	4.3	free radical production and deficit of oxidative phosphorylation shown in FRDA suggests that the mitochondrial respiration deficit may be amenable to
3951	FXN	frataxin	FRDA	4.3	Three FRDA patients were treated for 4 to 9 months with idebenone
3951	FXN	frataxin	FRDA	4.3	equal or more than 20% in 17 out of 38 FRDA patients 173 and by two more recent idebenone trials 174
3951	FXN	frataxin	FRDA	4.3	daily also resulted in decreased markers of oxidative stress in FRDA patients 176
3951	FXN	frataxin	FRDA	4.3	hypertrophy (LVH) LVH and ataxia has been evaluated in ten FRDA patients 177 After 6 months of therapy cardiac PCr to
3951	FXN	frataxin	FRDA	4.3	FRDA patients assessed neurologically using the semi-quantitative International Cooperative Ataxia Rating
26515	COQ10A	coenzyme Q10 homolog A (S. cerevisiae)	Q10	1.2	the efficacy of mitochondria-targeted and untargeted antioxidants derived from coenzyme Q10 and from vitamin E at preventing cell death due to
3951	FXN	frataxin	FRDA	4.3	oxidative stress has been recently investigated in cultured fibroblasts from FRDA patients in which glutathione synthesis have been blocked
3951	FXN	frataxin	FRDA	4.3	Targeted antioxidants may have therapeutic potential in FRDA and in other disorders involving mitochondrial oxidative damage
3951	FXN	frataxin	FRDA	4.3	Given the physiopathological mechanisms responsible for FRDA selenium administration could represent another therapy strategy
3951	FXN	frataxin	FRDA	4.3	address the toxicity of GPX mimetics in humans before human FRDA trials can be considered
3951	FXN	frataxin	FRDA	4.3	screening of compounds that have potential in the treatment of FRDA 183
3951	FXN	frataxin	FRDA	4.3	Since the discovery of the genetic basis of FRDA only few years ago the progress made in our understanding
3951	FXN	frataxin	FRDA	4.3	progress made in our understanding of the pathogenic mechanisms underlying FRDA has been remarkable
3951	FXN	frataxin	FRDA	4.3	the precise function of frataxin still remains to be defined FRDA has clearly been identified as a nuclear encoded mitochondrial disorder
3951	FXN	frataxin	FRDA	4.3	randomised trials which will confirm whether an early diagnosis of FRDA can be exploited to initiate antioxidant treatment and prevent the
3951	FXN	frataxin	frataxin	1.0	recent evidence suggests that frataxin might detoxify ros via activation of glutathione peroxidase and elevation of thiols and in addition that decreased expression of frataxin protein is associated with frda.
5013	HMOX1	heme oxygenase (decycling) 1	ho 1	1.0	among the various hsps hsp32 also known as heme oxygenase i ho 1 has received considerable attention as it has been recently demonstrated that ho 1 induction by generating the vasoactive molecule carbon monoxide and the potent antioxidant bilirubin could represent a protective system potentially active against brain oxidative injury.
17937	CUZD1	CUB and zona pellucida-like domains 1	erg 1	1.0	there is evidence to support that oxidative stress alters the expression of antioxidant enzymes and enhances expression and/or dna binding of numerous transcription factors including ap 1 fos jun myc erg 1 sapk and nfkb [3] .
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	ap 1	1.0	there is evidence to support that oxidative stress alters the expression of antioxidant enzymes and enhances expression and/or dna binding of numerous transcription factors including ap 1 fos jun myc erg 1 sapk and nfkb [3] .
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	however although activation of stress tolerance signaling leading to protective nuclear responses such as increased expression of heat shock proteins antioxidant enzymes and bcl 2 may be triggered to withstand all the above mentioned pathogenic changes a vicious cycle of increasing oxidative damage may insidiously develop over a period of years inducing progressive degenerativ
11740	TF	transferrin	transferrin	1.0	evated content of iron in specific areas of the human brain such as globus pallidus and substantia nigra sn while cerebrospinal fluid has very little iron binding capacity owing to its low content of transferrin; e cns contains non replicating neuronal cells which once damaged may be permanently dysfunctional or committed to programmed cell death apoptosis .
1516	CAT	catalase	catalase	1.0	ble substrates 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 glo
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	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
3951	FXN	frataxin	frataxin	1.0	there is now evidence to suggest that frataxin might detoxify ros via activation of glutathione peroxidase and elevation of thiols [10] and in addition that decreased expression of frataxin protein is associated with frda [11] .
3951	FXN	frataxin	friedreich ataxia	1.0	clinical and genetic features of friedreich ataxia
3951	FXN	frataxin	friedreich ataxia	1.0	friedreich ataxia is the commonest form of inherited ataxia with a frequency of 1 in 50 000 live births.
3951	FXN	frataxin	frataxin	1.0	mutations in the frda gene either gaa expansions or point mutations result in reduced expression of a protein called frataxin [16] which has been shown to be localized to mitochondria [16] [17] and [18] .
3951	FXN	frataxin	frataxin	1.0	the amount of residual frataxin in lymphoblastoid cell lines from frda patients correlates with the gaa expansion size in the smaller allele [16] and likely represents the molecular basis of the relationship between gaa expansion s
3951	FXN	frataxin	friedreich ataxia	1.0	there is significant evidence that the pathogenesis of several neurodegenerative diseases including parkinson's disease alzheimer's disease friedreich ataxia multiple sclerosis and amyotrophic lateral sclerosis may involve the generation of reactive oxygen species ros reactive nitrogen species rns and mitochondrial dysfunction.
3951	FXN	frataxin	frataxin	1.0	studies using the budding yeast saccharomyces cerevisiae have provided the first clues to understand the consequences of frataxin loss [17] [18] [19] [20] and [21] .
3951	FXN	frataxin	frataxin	1.0	it has been shown that deletion of the yeast frataxin homolog yfh1 results in a 10 fold increase in iron within the mitochondria along with increased ros production [17] and [20] .
3951	FXN	frataxin	frataxin	1.0	recent evidence suggests that frataxin might detoxify ros via activation of glutathione peroxidase and elevation of thiols [10] .
3951	FXN	frataxin	frataxin	1.0	transgenic overexpression of human frataxin increases cellular antioxidant defense via activation of glutathione peroxidase and elevation of reduced thiols thereby reducing the incidence of malignant transformation induced by ros as observed b
11180	SOD2	superoxide dismutase 2, mitochondrial	manganese superoxide dismutase	1.0	up regulation of protein manganese superoxide dismutase mnsod fails to occur in frda fibroblasts exposed to iron [25] .
3951	FXN	frataxin	frataxin	1.0	there is evidence that frataxin acts as a chaperone for fe ii and a storage compartment for excess iron [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] and [38] .
3951	FXN	frataxin	frataxin	1.0	this is consistent with the roles played by frataxin in iron export fe_amp_#x2013;s cluster assembly heme biosynthesis and prevention of oxidative stress.
3951	FXN	frataxin	frataxin	1.0	also frataxin plays a direct role in the mitochondrial energy activation and oxidative phosphorylation [11] .
3951	FXN	frataxin	frataxin	1.0	in mouse models deletion of the frataxin gene results in embryonic lethality [40] while its selective inactivation in neuronal and cardiac tissues leads to neurological symptoms and cardiomyopathy associated with mitochondrial iron_amp_#x20
3951	FXN	frataxin	frataxin	1.0	in contrast a model expressing 25_amp_#x2013;35% of wild type frataxin levels by virtue of a gaa 230 expansion inserted in the first intron of the mouse gene has no obvious phenotype [39] .
1991	CKB	creatine kinase, brain	creatine kinase	1.0	free metabolically active [adp] the major regulator of the oxidative phosphorylation can be calculated from the mrs data using the creatine kinase equilibrium expression [42] .
3951	FXN	frataxin	frataxin	1.0	the length of the gaa expansion has been shown to determine the amount of frataxin expressed [16] .
3951	FXN	frataxin	frataxin	1.0	therefore the residual expression of frataxin probably determines the reduced skeletal muscle mitochondrial atp production rate we detected in vivo.
31395	COX8B	cytochrome c oxidase, subunit 8B pseudogene	cytochrome c oxidase	1.0	other data are also consistent with these findings as it has been shown both in a patient with cytochrome c oxidase deficiency and in an animal model of copper deficiency that more than a 50% deficit in complex iv activity did not affect the respiratory flux [56] .
2898	DLD	dihydrolipoamide dehydrogenase	diaphorase	1.0	excessive formation of no_amp_#xb7; from glial origin has been evidenced in some study in which nadph diaphorase a cytochemical marker of nos activity positive glial cells have been identified in the substantia nigra of postmortem brains obtained from individuals with parkinson's disease [88] .
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	nitric oxide synthase	1.0	the enzyme responsible for no synthesis is the nitric oxide synthase nos family of enzymes which catalyse the conversion of arginine to citrulline and no.
5991	IL1A	interleukin 1, alpha	interleukin 1	1.0	activation of inos requires gene transcription and the induction can be influenced by endotoxin and cytokines interleukin 1 interleukin 2 lipopolysaccharide interferon _amp_#x3b3; tumor necrosis factor .
6001	IL2	interleukin 2	interleukin 2	1.0	activation of inos requires gene transcription and the induction can be influenced by endotoxin and cytokines interleukin 1 interleukin 2 lipopolysaccharide interferon _amp_#x3b3; tumor necrosis factor .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tumor necrosis factor	1.0	activation of inos requires gene transcription and the induction can be influenced by endotoxin and cytokines interleukin 1 interleukin 2 lipopolysaccharide interferon _amp_#x3b3; tumor necrosis factor .
5962	IL10	interleukin 10	interleukin 10	1.0	this activation can be blocked by anti inflammatory drugs dexamethasone inhibitory cytokines interleukin 4 interleukin 10 prostaglandins pga 2 tissue growth factors or inhibitors of protein synthesis e.g. cycloheximide [94] .
6014	IL4	interleukin 4	interleukin 4	1.0	this activation can be blocked by anti inflammatory drugs dexamethasone inhibitory cytokines interleukin 4 interleukin 10 prostaglandins pga 2 tissue growth factors or inhibitors of protein synthesis e.g. cycloheximide [94] .
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	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.
399	ALB	albumin	serum albumin	1.0	nitrosothiols with biological relevance have been isolated and characterized including s nitrosoglutathione and the nitrosothiols of serum albumin [101] .
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	glyceraldehyde 3 phosphate dehydrogenase	1.0	no has been demonstrated to stimulate the auto adp ribosylation of glyceraldehyde 3 phosphate dehydrogenase gapdh by reacting with a critical cysteine with resulting binding of nad to the catalytic cysteine inhibition of gapdh activity and depression of glycolysis [104] .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	other heme protein targets for no are catalase cytochrome c hemoglobin and peroxidase.
1516	CAT	catalase	catalase	1.0	other heme protein targets for no are catalase cytochrome c hemoglobin and peroxidase.
10451	RRM1	ribonucleotide reductase M1	ribonucleotide reductase	1.0	through this mechanism no a irreversibly inactivates the enzyme ribonucleotide reductase thereby inhibiting dna synthesis b moves iron from iron storage proteins such as ferritin and c mobilizes cu+ from caeruloplasmin and metallothionein.
11180	SOD2	superoxide dismutase 2, mitochondrial	manganese superoxide dismutase	1.0	the factors responsible for this include the inner mitochondrial membrane lipid composition and/or the oxidant/antioxidant balance particularly manganese superoxide dismutase and/or heat shock protein activity and expressions as well as the glutathione status.
25806	GSTCD	glutathione S-transferase, C-terminal domain containing	glutathione s transferase	1.0	this reaction can occur spontaneously but most often is catalyzed by glutathione s transferase.
4341	GLUL	glutamate-ammonia ligase (glutamine synthetase)	glutamine synthetase	1.0	the latter finding that could also be induced by addition of a_amp_#x3b2; to synaptosomes [127] coupled with the reported loss of glutamine synthetase activity in ad brain [127] suggests that glutamate stimulated excitotoxic mechanisms could be important in neurodegeneration in ad.
3951	FXN	frataxin	friedreich ataxia	1.0	there are evidences of an impairment in vivo of glutathione homeostasis and antioxidant enzymes in patients with friedreich ataxia suggesting a relevant role of free radical cytotoxicity in the pathophysiology of the disease.
3951	FXN	frataxin	friedreich ataxia	1.0	in fact a reduction of free glutathione levels in the blood of patients with friedreich ataxia a total glutathione concentration comparable to the controls and a significant increase of glutathione bound to haemoglobin in erythrocytes have been demonstrated in frda patients [128] also associat
4638	GSTP1	glutathione S-transferase pi	glutathione transferase	1.0	in 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] .
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	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] .
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	some of the known hsps include ubiquitin hsp10 hsp27 hsp32 or ho 1 hsp47 hsp60 hsc70 hsp70 or hsp72 hsp90 and hsp100/105.
10417	RPS27A	ribosomal protein S27a	ubiquitin	1.0	some of the known hsps include ubiquitin hsp10 hsp27 hsp32 or ho 1 hsp47 hsp60 hsc70 hsp70 or hsp72 hsp90 and hsp100/105.
5013	HMOX1	heme oxygenase (decycling) 1	ho 1	1.0	some of the known hsps include ubiquitin hsp10 hsp27 hsp32 or ho 1 hsp47 hsp60 hsc70 hsp70 or hsp72 hsp90 and hsp100/105.
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	hsp70 .
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	included in this family are hsc70 heat shock cognate the constitutive form hsp70 the inducible form also referred to as hsp72 grp75 a constitutively expressed glucose regulated protein found in the endoplasmic reticulum .
4646	GTF2A1	general transcription factor IIA, 1, 19/37kDa	glucose regulated protein	1.0	included in this family are hsc70 heat shock cognate the constitutive form hsp70 the inducible form also referred to as hsp72 grp75 a constitutively expressed glucose regulated protein found in the endoplasmic reticulum .
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	after a variety of central nervous system cns insults hsp70 is synthesized at high levels and is present in the cytosol nucleus and endoplasmic reticulum .
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	after heat shock for instance the synthesis of hsp70 increases to a point to where it becomes the most abundant single protein in a cell.
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	once synthesized hsp70 binds to denaturated proteins in an atp dependent manner.
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	only recently however with the availability of transgenic animals and gene transfer has become possible to overexpress the gene encoding hsp70 to test directly the hypothesis that stress proteins protects cells from injury and it has been demonstrated that overproduction of hsp70 leads to protection in several different models of nervous sy
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	to test directly the hypothesis that stress proteins protects cells from injury and it has been demonstrated that overproduction of hsp70 leads to protection in several different models of nervous system injury [136] and [137] .
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	following focal cerebral ischemia mrna encoding hsp70 is synthesized in most ischemic cells except in areas of very low blood flow because of limited atp levels.
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	hsp70 proteins is produced mainly in endothelial cells in the core of infarcts in the cells that are most resistant to ischemia in glial cells at the edges of infarcts and in neurons outside the areas of i
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	it has been suggested that this neuronal expression of hsp70 outside an infarct can be used to define the ischemic penumbras which means the zone of protein denaturation in the ischemic areas [138] .
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	transfection of cultured astrocytes with hsp70 protects them from ischemia or glucose deprivation [140] .
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	hsp70 has been demonstrated to inhibit caspase 3 activation caused by ceramide and also affect jun kinase and p38 kinase activation [141] .
6886	MAPK9	mitogen-activated protein kinase 9	jun kinase	1.0	hsp70 has been demonstrated to inhibit caspase 3 activation caused by ceramide and also affect jun kinase and p38 kinase activation [141] .
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	hsp70 has been demonstrated to inhibit caspase 3 activation caused by ceramide and also affect jun kinase and p38 kinase activation [141] .
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	in addition hsp70 binds to and modulates the function of bag 1 the bcl 2 binding protein [142] thus modulating some type of apoptosis related cell death.
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	in addition hsp70 binds to and modulates the function of bag 1 the bcl 2 binding protein [142] thus modulating some type of apoptosis related cell death.
939	BAG3	BCL2-associated athanogene 3	bcl 2 binding protein	1.0	in addition hsp70 binds to and modulates the function of bag 1 the bcl 2 binding protein [142] thus modulating some type of apoptosis related cell death.
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	we have demonstrated in astroglial cell cultures that cytokine induced nitrosative stress is associated with an increased synthesis of hsp70 stress proteins.
5232	HSPA1A	heat shock 70kDa protein 1A	hsp70	1.0	increase in hsp70 protein expression was also found after treatment of cells with the no generating compound sodium nitroprusside snp thus suggesting a role for no in inducing hsp70 proteins.
10417	RPS27A	ribosomal protein S27a	ubiquitin	1.0	ubiquitin is one of the smallest hsps and is expressed throughout brain in response to ischemia.
3415	EPO	erythropoietin	erythropoietin	1.0	it is involved in targeting and chaperoning of proteins degraded in proteasomes which include nfkb cyclins hsfs hypoxia inducible factor some apoptosis related proteins tumor necrosis factor and erythropoietin receptors [146] .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tumor necrosis factor	1.0	it is involved in targeting and chaperoning of proteins degraded in proteasomes which include nfkb cyclins hsfs hypoxia inducible factor some apoptosis related proteins tumor necrosis factor and erythropoietin receptors [146] .
4235	GFAP	glial fibrillary acidic protein	glial fibrillary acidic protein	1.0	it chaperones cytoskeletal proteins such as intermediate filaments actin or glial fibrillary acidic protein following stress in astrocytes.
11920	FAS	Fas (TNF receptor superfamily, member 6)	apo 1	1.0	it also protects against fas apo 1 staurosporine tnf and etoposside induced apoptotic cell death as well as h 2 o 2 induced necrosis [147] .
4646	GTF2A1	general transcription factor IIA, 1, 19/37kDa	glucose regulated protein	1.0	hsp60 glucose regulated protein 75 grp75 and hsp10 chaperone proteins within mitochondria.
5013	HMOX1	heme oxygenase (decycling) 1	ho 1	1.0	there are three isoforms of heme oxygenase: ho 1 or inducible isoform ho 2 or constitutive isoform and the recently discovered ho 3 [149] [150] [151] [152] [153] and [154] .
5014	HMOX2	heme oxygenase (decycling) 2	ho 2	1.0	there are three isoforms of heme oxygenase: ho 1 or inducible isoform ho 2 or constitutive isoform and the recently discovered ho 3 [149] [150] [151] [152] [153] and [154] .
5013	HMOX1	heme oxygenase (decycling) 1	ho 1	1.0	the iron released by ho 1 is bound by ferritin perhaps via a ho 1 chaperone function [155] .
5013	HMOX1	heme oxygenase (decycling) 1	ho 1	1.0	increasing evidence suggests that the ho 1 gene is redox regulated and contains in its promoter region the antioxidant responsive element are similar to other antioxidant enzymes.
5013	HMOX1	heme oxygenase (decycling) 1	ho 1	1.0	significant increases in the levels of ho 1 have been observed in ad brains in association with neurofibrillary tangles [157] and ho 1 mrna was found to be increased in ad neocortex and cerebral vessels [158] .
4235	GFAP	glial fibrillary acidic protein	glial fibrillary acidic protein	1.0	ho 1 increase was not only in association with neurofibrillary tangles but also co localized with senile plaques and glial fibrillary acidic protein positive astrocytes in ad brains [153] .
5013	HMOX1	heme oxygenase (decycling) 1	ho 1	1.0	ho 1 increase was not only in association with neurofibrillary tangles but also co localized with senile plaques and glial fibrillary acidic protein positive astrocytes in ad brains [153] .
5013	HMOX1	heme oxygenase (decycling) 1	ho 1	1.0	it is conceivable that the dramatic increase in ho 1 in ad may be a direct response to increased free heme associated with neurodegeneration and an attempt to convert the highly damaging heme into the antioxidants biliverdin and bilirubin.
5013	HMOX1	heme oxygenase (decycling) 1	heme oxygenase 1	1.0	heme oxygenase 1 is rapidly upregulated by oxidative and nitrosative stresses as well as by glutathione depletion.
5013	HMOX1	heme oxygenase (decycling) 1	ho 1	1.0	remarkably recent evidence has demonstrated that curcumin is a potent inducer of ho 1 in vascular endothelial cells [7] and [167] .
5013	HMOX1	heme oxygenase (decycling) 1	ho 1	1.0	we have also recently demonstrated in astroglial cells the role of caffeic acid phenylethyl ester cape an active component of propolis as a novel ho 1 inducer [162] .
2244	COQ7	coenzyme Q7 homolog, ubiquinone (yeast)	coenzyme q	1.0	the effect of another antioxidant treatment coenzyme q 10 400 mg/day plus vitamin e 2100 iu/day on in vivo cardiac and calf muscle energy metabolism left ventricle hypertrophy lvh and ataxia has been evaluated in ten frda patients [177] after 6 months of
3951	FXN	frataxin	friedreich ataxia	1.0	a deficiency of the micronutrient has also been reported in patients with friedreich ataxia and there are histological similarities between friedreich's cardiomyopathy and keshan disease.
3951	FXN	frataxin	friedreich ataxia	1.0	as iron induced mitochondrial oxidative damage is central to the pathology of friedreich ataxia and in addition some studies suggest a link between frataxin expression glutathione peroxidase gpx activity and oxidative stress the administration of selenium supplements could normalize the antioxi
3951	FXN	frataxin	frataxin	1.0	as iron induced mitochondrial oxidative damage is central to the pathology of friedreich ataxia and in addition some studies suggest a link between frataxin expression glutathione peroxidase gpx activity and oxidative stress the administration of selenium supplements could normalize the antioxidant activity of myocardial glutathione peroxidase and slow t
3951	FXN	frataxin	frataxin	1.0	although the precise function of frataxin still remains to be defined frda has clearly been identified as a nuclear encoded mitochondrial disorder.