SciMiner Result Report Page

Document Information

PMID	15210305 ( )
Title	Spinal cord molecular profiling provides a better understanding of amyotrophic lateral sclerosis pathogenesis.
Abstract	Research efforts in amyotrophic lateral sclerosis (ALS) have not yet provided a comprehensive explanation of the disease pathogenesis, which is emerging as a complex interaction between multiple factors. Gene expression studies traditionally based on single mRNA specie analysis have recently progressed to allow entire transcriptional profiles of affected tissues to be obtained through array-based methods. This experimental approach has significantly improved our understanding of the molecular changes occurring in ALS, although its limitations in the detection of low-abundance transcripts in tissues with a high level of complexity are becoming increasingly recognized. In this paper, experimental findings based on an expression study in post-mortem spinal cord from sporadic ALS individuals will be discussed in light of recently published data using array analysis in an animal model of the disease. Previous expression data obtained using conventional techniques are also compared. Through the analysis of the information arising from ALS post-mortem and animal model tissues studies, we have identified a pattern of molecular events in which factors implicated in the immune response, cytoprotection and growth-differentiation are differentially regulated in a time-dependent way from early to advanced stages of disease progression. Psychological Medicine, Faculty of Medicine, Imperial College London, Charing Cross Hospital, London W14 8RF, UK. a.malaspina@ic.uk

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
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	24	SOD1 \| ALS1 \| superoxide dismutase \|
2482	CSTB	cystatin B (stefin B)	14	stefin b \| CSTB \| cystatin b \| EPM1 \| STFB \|
2169	CNTF	ciliary neurotrophic factor	7	CNTF \| ciliary neurotrophic factor \| CNTF-deficient \|
12680	VEGFA	vascular endothelial growth factor A	7	VEGF \|
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	7	COX-2 \| cox 2 \|
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	6	APP \| amyloid \|
5995	IL1RAP	interleukin 1 receptor accessory protein	6	IL-1RAcP \| il 1racp \|
6204	JUN	jun oncogene	5	c-jun \| c jun \|
9919	RBP1	retinol binding protein 1, cellular	4	CRBP1 \| CRBP \| retinol binding protein1 \|
12435	TXN	thioredoxin	4	thioredoxin \|
14922	HRASLS	HRAS-like suppressor	4	h rev107 \| H-REV107-like \|
10940	SLC1A2	solute carrier family 1 (glial high affinity glutamate transporter), member 2	4	excitatory amino acid transporter 2 \| EAAT2 \|
2641	CYP46A1	cytochrome P450, family 46, subfamily A, polypeptide 1	3	cholesterol 24 hydroxylase \| CYP46 \|
4601	GRN	granulin	3	granulin \|
613	APOE	apolipoprotein E	3	apolipoprotein e \| ApoE \|
10632	CCL5	chemokine (C-C motif) ligand 5	3	RANTES \|
5992	IL1B	interleukin 1, beta	3	IL-1 \| il 1 \| IL1beta \|
11556	TAL1	T-cell acute lymphocytic leukemia 1	2	TAL-1 \| tal 1 \|
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	2	nf kappa b \|
10618	CCL2	chemokine (C-C motif) ligand 2	2	mcp 1 \| MCP-1 \|
3562	FABP7	fatty acid binding protein 7, brain	2	b fabp \| B-FABP \|
6881	MAPK8	mitogen-activated protein kinase 8	2	JNK \|
990	BCL2	B-cell CLL/lymphoma 2	2	Bcl-2 \| bcl 2 \|
1907	CH25H	cholesterol 25-hydroxylase	2	cholesterol 25 hydroxylase \|
5991	IL1A	interleukin 1, alpha	2	IL1alpha \| interleukin 1 \|
7634	NAIP	NLR family, apoptosis inhibitory protein	2	neuronal apoptosis inhibitory protein \| NAIP \|
7897	NPC1	Niemann-Pick disease, type C1	2	NP-C \|
2197	COL1A1	collagen, type I, alpha 1	2	collagen \|
6011	IL3	interleukin 3 (colony-stimulating factor, multiple)	2	IL3 \| interleukin 3 \|
6893	MAPT	microtubule-associated protein tau	2	tau protein \|
2170	CNTFR	ciliary neurotrophic factor receptor	2	cntfr alpha \|
992	BCL2L1	BCL2-like 1	2	bcl xl \|
2095	CLU	clusterin	2	clusterin \| apoJ \|
6014	IL4	interleukin 4	2	IL4 \|
11881	TMSB4X	thymosin beta 4, X-linked	2	thymosin beta 4 \| prothymosin beta 4 \|
644	AR	androgen receptor (dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease)	2	androgen receptor \| SBMA \|
4140	GAP43	growth associated protein 43	2	growth associated protein 43 \| GAP43 \|
9508	PSEN1	presenilin 1 (Alzheimer disease 3)	2	PS1 \| presenilin 1 \|
443	ALS2	amyotrophic lateral sclerosis 2 (juvenile)	1	ALS2 \|
445	SETX	senataxin	1	ALS4 \|
6886	MAPK9	mitogen-activated protein kinase 9	1	SAPK \|
6664	LOX	lysyl oxidase	1	lysyl oxidase \|
6547	LDLR	low density lipoprotein receptor (familial hypercholesterolemia)	1	LDL-r \|
936	BAD	BCL2-antagonist of cell death	1	BAD \|
6321	KIF3C	kinesin family member 3C	1	KIF3C \|
2348	CREBBP	CREB binding protein (Rubinstein-Taybi syndrome)	1	creb binding protein \|
6149	ITGAM	integrin, alpha M (complement component 3 receptor 3 subunit)	1	CD11B \|
1242	C1QB	complement component 1, q subcomponent, B chain	1	C1qB \|
3769	FMO1	flavin containing monooxygenase 1	1	FMO1 \|
6001	IL2	interleukin 2	1	IL2 \|
4879	HEXB	hexosaminidase B (beta polypeptide)	1	hexosaminidase b \|
3665	FGF1	fibroblast growth factor 1 (acidic)	1	aFGF \|
5173	HRAS	v-Ha-ras Harvey rat sarcoma viral oncogene homolog	1	HRAS \|
4235	GFAP	glial fibrillary acidic protein	1	GFAP \|
3684	FGF6	fibroblast growth factor 6	1	FGF-6 \|
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	1	caspase 3 \|
2345	CREB1	cAMP responsive element binding protein 1	1	CREB-binding \|
5993	IL1R1	interleukin 1 receptor, type I	1	IL1RA \|
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	1	cysteine protease \|
9449	PRNP	prion protein (p27-30) (Creutzfeldt-Jakob disease, Gerstmann-Strausler-Scheinker syndrome, fatal familial insomnia)	1	prion protein prp \|
5438	IFNG	interferon, gamma	1	IFN-gamma \|
3238	EGR1	early growth response 1	1	zif 268 \|
1774	CDK5	cyclin-dependent kinase 5	1	cyclin dependent kinase 5 \|
1678	CD4	CD4 molecule	1	CD4 \|
3581	BPTF	bromodomain PHD finger transcription factor	1	FAC1 \|
7808	NGF	nerve growth factor (beta polypeptide)	1	NGF \|

Targets by SciMiner Full list

HUGO ID	Symbol	Name	ActualStr	Score	FlankingText
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	ALS1	2.9	The first ALS locus (ALS1) ALS1 to be identified on chromosome 21 contains the cytosolic copper_amp_#x2013
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	chromosome 21 contains the cytosolic copper_amp_#x2013 zinc superoxide dismutase (SOD1) SOD1 gene which has been found to harbour at least 100
443	ALS2	amyotrophic lateral sclerosis 2 (juvenile)	ALS2	1.5	In the case of the chromosome 2 locus (ALS2), ALS2 mutations in a putative GTPase (the the alsin gene have
12680	VEGFA	vascular endothelial growth factor A	VEGF	2.8	The potential role of the vascular endothelial growth gene (VEGF) VEGF as a risk/causitive risk causitive factor in ALS has been
12680	VEGFA	vascular endothelial growth factor A	VEGF	2.8	VEGF induction occurs following the binding of hypoxia-inducible factors to the
12680	VEGFA	vascular endothelial growth factor A	VEGF	2.8	VEGF coding region analysis has failed to identify mutations in ALS
12680	VEGFA	vascular endothelial growth factor A	VEGF	2.8	of Swedish Belgian and English patients has revealed a specific VEGF haplotype in the promoter region which is associated with a
12680	VEGFA	vascular endothelial growth factor A	VEGF	2.8	1.8 times greater risk of ALS and with lowered circulating VEGF levels in vivo 31 and 50
7634	NAIP	NLR family, apoptosis inhibitory protein	NAIP	0.6	motor neuron (SMN) SMN and neuronal apoptosis inhibitory protein (NAIP) NAIP 79
2169	CNTF	ciliary neurotrophic factor	CNTF	1.9	Recently Ciliary Neurotrophic factor (CNTF) CNTF has been proposed as a modifier gene since the rare
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	age of onset of disease in FALS cases carrying a SOD1 mutation
2169	CNTF	ciliary neurotrophic factor	CNTF-deficient	1.9	Similarly when CNTF-deficient mice are crossed with SOD1 G93A transgenic mice an earlier
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	Similarly when CNTF-deficient mice are crossed with SOD1 G93A transgenic mice an earlier age of onset has been
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	post-mortem tissue and tissues taken from animal models (G93 G93 SOD1 transgenic mouse of ALS have been investigated
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	With the discovery of SOD1 gene mutations oxidative stress has gained momentum as a major
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	The cytosolic SOD1 protein has a widespread expression in different human tissues and
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	Human motor neurones show high levels of expression of SOD1 proteins compared to others neurones and this may reflect a
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	It has been proposed that SOD1 may be crtical for motor neurones in stressful conditions but
10940	SLC1A2	solute carrier family 1 (glial high affinity glutamate transporter), member 2	EAAT2	1.3	receptors and of the excitatory amino acid transporter 2 (EAAT2) EAAT2 (which which is involved in the removal of glutamate from
3769	FMO1	flavin containing monooxygenase 1	FMO1	0.9	events include thioredoxin lysyl oxidase (LO), LO flavin-containing monooxygenase (FMO1), FMO1 interleukin I receptor accessory protein (IL-1RAcP) IL-1RAcP and a transcript
5995	IL1RAP	interleukin 1 receptor accessory protein	IL-1RAcP	1.3	flavin-containing monooxygenase (FMO1), FMO1 interleukin I receptor accessory protein (IL-1RAcP) IL-1RAcP and a transcript representing a possible 14-3-3 spinal-cord isoform 59
2197	COL1A1	collagen, type I, alpha 1	collagen	0.3	copper-dependent enzyme that catalyses the synthesis reaction of hydroxylysine in collagen biosynthesis
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	slowing of axonal transport is an important feature in mutant SOD1 mice 111 where NF aggregates are detected which affect transport
4235	GFAP	glial fibrillary acidic protein	GFAP	0.6	GFAP up-regulation is not uncommonly seen in expression studies reflecting reactive
2197	COL1A1	collagen, type I, alpha 1	collagen	0.3	The relationship between the metabolic alteration of collagen taking place in the skin and serum of ALS patients
12680	VEGFA	vascular endothelial growth factor A	VEGF	2.8	An increase of VEGF levels in serum but not in homogenates of spinal cord
12680	VEGFA	vascular endothelial growth factor A	VEGF	2.8	during the course of the disease process generating a time-dependent VEGF tissue response 74
6204	JUN	jun oncogene	c-jun	2.4	Immunohistochemical expression of a number of gene candidates including c-jun JNK/SAPK JNK SAPK (a a kinase that exerts a stress-related
6881	MAPK8	mitogen-activated protein kinase 8	JNK	0.3	expression of a number of gene candidates including c-jun JNK/SAPK JNK SAPK (a a kinase that exerts a stress-related activation of
6886	MAPK9	mitogen-activated protein kinase 9	SAPK	1.3	of a number of gene candidates including c-jun JNK/SAPK JNK SAPK (a a kinase that exerts a stress-related activation of c-jun
6204	JUN	jun oncogene	c-jun	2.4	SAPK (a a kinase that exerts a stress-related activation of c-jun and NF-kappa B a transcription factor induced by oxidative injury
6881	MAPK8	mitogen-activated protein kinase 8	JNK	0.3	The JNK/SAPK-c-Jun JNK SAPK-c-Jun pathway was found to be markedly up-regulated 67 in
2482	CSTB	cystatin B (stefin B)	STFB	4.6	was found to have a high homology with Stefin B STFB also called cystatin B (CSTB)], CSTB which is a member
2482	CSTB	cystatin B (stefin B)	CSTB	4.6	homology with Stefin B STFB also called cystatin B (CSTB)], CSTB which is a member of the superfamily of non-caspase cysteine
2482	CSTB	cystatin B (stefin B)	EPM1	4.6	of progressive myoclonus epilepsy of the Unverricht_amp_#x2013 Lundborg type (EPM1) EPM1 are caused by mutations (mostly mostly an expansion of a
2482	CSTB	cystatin B (stefin B)	EPM1	4.6	EPM1 is an autosomal recessive disorder characterized by seizures myoclonus and
2482	CSTB	cystatin B (stefin B)	EPM1	4.6	cystatin B mRNA down-regulation in various tissues from patients with EPM1 49
2482	CSTB	cystatin B (stefin B)	EPM1	4.6	spinal cord involvement such as spinal or segmental myoclonus in EPM1 and paralysis with muscle wasting in ALS
2169	CNTF	ciliary neurotrophic factor	CNTF	1.9	CNTF initially reported as a potent survival factor in spinal motor
2169	CNTF	ciliary neurotrophic factor	CNTF	1.9	CNTF expression was down-regulated in the lateral corticospinal tracts of spinal
2169	CNTF	ciliary neurotrophic factor	CNTF	1.9	compared to control particularly in those patients exhibiting a specific CNTF null allele 77
2169	CNTF	ciliary neurotrophic factor	CNTF	1.9	However genotyping of the CNTF receptor alpha (CNTFR-alpha) CNTFR-alpha has failed to show any significant
3665	FGF1	fibroblast growth factor 1 (acidic)	aFGF	2.2	Acidic fibroblast growth factor (aFGF) aFGF has been investigated in anterior horn cells of spinal cord
3581	BPTF	bromodomain PHD finger transcription factor	FAC1	1.0	FAC1 a protein known to play a key role in the
4140	GAP43	growth associated protein 43	GAP43	0.6	from ALS spinal cord applies to growth-associated protein 43 (GAP43), GAP43 a phosphoprotein which is expressed during neurite elongation 42
644	AR	androgen receptor (dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease)	SBMA	1.6	motor system is exemplified by spinal bulbar muscular atrophy (SBMA), SBMA a condition in which a clinical picture of motor neurone
14922	HRASLS	HRAS-like suppressor	H-REV107-like	2.3	Another hormone sensitive transcript with high homology to rat H-REV107-like protein was found to be significantly up-regulated in ALS spinal
5173	HRAS	v-Ha-ras Harvey rat sarcoma viral oncogene homolog	HRAS	0.3	II tumour suppressor as shown by its reversible down-regulation in HRAS transformed cell line 99
9919	RBP1	retinol binding protein 1, cellular	CRBP1	3.1	Cellular retinol-binding protein1 (CRBP1) CRBP1 showed a marked up-regulation in ALS spinal cord 60
9919	RBP1	retinol binding protein 1, cellular	CRBP	3.1	Cellular retinoid-binding proteins (CRBP) CRBP have a privileged distribution in the ventral region (motor motor
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	reduces neuronal reactive oxygen species (ROS) ROS content and enhances SOD1 protein levels during staurosporine-induced apoptosis in primary cultures from neonatal
7808	NGF	nerve growth factor (beta polypeptide)	NGF	0.6	In addition RA potentiates the protective effect of NGF in a model of stautosporine-induced apoptosis in cultured chick neurones
9919	RBP1	retinol binding protein 1, cellular	CRBP1	3.1	The marked up-regulation of the CRBP1 in ALS spinal cord and of the retinoid receptor subunit
2345	CREB1	cAMP responsive element binding protein 1	CREB-binding	2.1	et al 115 which shows a significant up-regulation of a CREB-binding protein in the G93A transgenic (TG) TG animal model
10618	CCL2	chemokine (C-C motif) ligand 2	MCP-1	1.6	beta deposition activates astrocytes and oligodendrocytes to produce chemokines (MCP-1 MCP-1 and RANTES which act as potent in vitro microglial and
10632	CCL5	chemokine (C-C motif) ligand 5	RANTES	1.6	activates astrocytes and oligodendrocytes to produce chemokines (MCP-1 MCP-1 and RANTES which act as potent in vitro microglial and macrophage chemoattractants
1242	C1QB	complement component 1, q subcomponent, B chain	C1qB	0.3	C1qB clusterin (apoJ) apoJ and the T-cell receptor (TCR) TCR transcript
2095	CLU	clusterin	apoJ	2.0	C1qB clusterin (apoJ) apoJ and the T-cell receptor (TCR) TCR transcript have been found
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX-2	2.0	COX-2 and CD11B (a a specific marker of microglia activation have
6149	ITGAM	integrin, alpha M (complement component 3 receptor 3 subunit)	CD11B	1.0	COX-2 and CD11B (a a specific marker of microglia activation have been reported
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX-2	2.0	The significant up-regulation of COX-2 in ALS spinal cord compared to control tissues including patients
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX-2	2.0	COX-2 mRNA up-regulation was restricted to pathologically affected tissue and this
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX-2	2.0	to pathologically affected tissue and this was accompanied by increased COX-2 protein levels
5995	IL1RAP	interleukin 1 receptor accessory protein	IL-1RAcP	1.3	Interleukin I receptor accessory protein (IL-1RAcP) IL-1RAcP mRNA markedly over-expressed in ALS spinal cord is a trans-membrane
5992	IL1B	interleukin 1, beta	IL-1	1.3	receptor complex which binds to the pro-inflammatory protein interleukin-1 (IL-1) IL-1 14
5995	IL1RAP	interleukin 1 receptor accessory protein	IL-1RAcP	1.3	IL-1RAcP has also been found to be up-regulated in spinal cord
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	also been found to be up-regulated in spinal cord from SOD1 G93A transgenic mice 76
10632	CCL5	chemokine (C-C motif) ligand 5	RANTES	1.6	The small inducible cytokine (RANTES) RANTES mRNA was also found in the GDA study to be
1678	CD4	CD4 molecule	CD4	0.3	subfamily of chemokines that function as a pro-inflammatory chemoattractant for CD4 T cells monocytes and eosinophils and as an activator of
10632	CCL5	chemokine (C-C motif) ligand 5	RANTES	1.6	Like other members of the chemokine superfamily RANTES has been implicated in a number of chronic inflammatory and
2641	CYP46A1	cytochrome P450, family 46, subfamily A, polypeptide 1	CYP46	2.8	by a recent study on cholesterol 24-hydroxylase encoded by the CYP46 gene
2641	CYP46A1	cytochrome P450, family 46, subfamily A, polypeptide 1	CYP46	2.8	A CYP46 polymorphism is associated with an increased beta-amyloid load in brain
6893	MAPT	microtubule-associated protein tau	tau	0.8	tissues increased cerebrospinal fluid levels of beta-amyloid peptides/phosphorylated peptides phosphorylated tau protein and to a higher risk of late onset sporadic
7897	NPC1	Niemann-Pick disease, type C1	NP-C	0.3	neurovisceral lipid storage disorder Niemann_amp_#x2013 Pick type C disease (NP-C) NP-C 84
7897	NPC1	Niemann-Pick disease, type C1	NP-C	0.3	NP-C is a neurodevelopmental disorder characterized by progressive neurodegeneration and lysosomal
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	in spinal cord of transgenic mouse models with the G93A SOD1 gene mutation 37 76 and 115 the molecular profiling of
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	In SOD1 G93A mice the timing of behavioural and pathological changes appears
5991	IL1A	interleukin 1, alpha	IL1alpha	0.3	study demonstrates the over-expression of a subset of cytokines including IL1alpha IL1beta and IL1RA at 80 days undergoing a significant increase
5992	IL1B	interleukin 1, beta	IL1beta	1.3	demonstrates the over-expression of a subset of cytokines including IL1alpha IL1beta and IL1RA at 80 days undergoing a significant increase by
5993	IL1R1	interleukin 1 receptor, type I	IL1RA	1.3	over-expression of a subset of cytokines including IL1alpha IL1beta and IL1RA at 80 days undergoing a significant increase by 120 days
6001	IL2	interleukin 2	IL2	0.3	by 120 days whereas T-cell derived cytokines (lymphokines) lymphokines including IL2 IL3 and IL4 are not differentially expressed at these time
6011	IL3	interleukin 3 (colony-stimulating factor, multiple)	IL3	0.6	120 days whereas T-cell derived cytokines (lymphokines) lymphokines including IL2 IL3 and IL4 are not differentially expressed at these time points
6014	IL4	interleukin 4	IL4	0.3	120 days whereas T-cell derived cytokines (lymphokines) lymphokines including IL2 IL3 and IL4 are not differentially expressed at these time points
6014	IL4	interleukin 4	IL4	0.3	whereas T-cell derived cytokines (lymphokines) lymphokines including IL2 IL3 and IL4 are not differentially expressed at these time points
10940	SLC1A2	solute carrier family 1 (glial high affinity glutamate transporter), member 2	EAAT2	1.3	expression studies have highlighted the early focal loss of the EAAT2 glutamate transporter in the ventral horn of the G93A TG
10940	SLC1A2	solute carrier family 1 (glial high affinity glutamate transporter), member 2	EAAT2	1.3	pattern of steady increase of gliosis paralleled with a 90% EAAT2 loss in the ventral horn is also reported suggesting a
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.0	Towards the end stage of the disease Bcl-2 and Bcl-XL proteins acting as apoptosis inhibitors show reduced expression
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	stem cortex and in Purkinje cells of the cerebellum in SOD1 mutant animals 52
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	hypoglossal nerve injury and in erythrocytes of FALS cases with SOD1 mutations 60 61 and 75
14922	HRASLS	HRAS-like suppressor	H-REV107-like	2.3	in the post-mortem study such as the human homologue of H-REV107-like protein are known to have an intrinsic anti-proliferative activity 41
11556	TAL1	T-cell acute lymphocytic leukemia 1	TAL-1	1.6	anti-proliferative activity 41 or as in the case of the TAL-1 proto-oncogene to increase cell proliferation via an anti-apoptotic effect
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	The study of SOD1 G93A transgenic mice by Olsen et al 76 identified a
613	APOE	apolipoprotein E	ApoE	1.3	Apolipoprotein E (ApoE) ApoE and (to to a lesser extent Apo D gene expression
3562	FABP7	fatty acid binding protein 7, brain	B-FABP	2.5	include Hexosaminidase B and brain fatty acid binding protein (B-FABP), B-FABP the latter acting as a molecular scavenger binding to oxidized
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	may also account for diversities in the molecular profile between SOD1 animal models and human tissue studies
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	a markedly increased expression in spinal cord astrocytes of G93A SOD1 transgenic mice particularly in the early stage of disease whereas
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	abnormal copper homeostasis may reflect the activity of the mutated SOD1 enzyme
6321	KIF3C	kinesin family member 3C	KIF3C	0.6	an early stage of the disease in TG mice include KIF3C which is involved in axonal transport and highlights the early
6547	LDLR	low density lipoprotein receptor (familial hypercholesterolemia)	LDL-r	0.6	impaired axonal transport in the development of ALS 111 and LDL-r which is involved in lipid metabolism
3684	FGF6	fibroblast growth factor 6	FGF-6	1.2	FGF-6 is significantly up-regulated at 80 days but its expression decreases
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.6	of AD pathology possibly established and maintained by a significant amyloid beta deposition
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.6	The amyloid precursor protein/presenilin-1 protein presenilin-1 (APP+PS1) APP PS1 transgenic mouse is
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	APP	0.6	The amyloid precursor protein/presenilin-1 protein presenilin-1 (APP+PS1) APP PS1 transgenic mouse is a model for amyloid deposition and
9508	PSEN1	presenilin 1 (Alzheimer disease 3)	PS1	0.6	The amyloid precursor protein/presenilin-1 protein presenilin-1 (APP+PS1) APP PS1 transgenic mouse is a model for amyloid deposition and as
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.6	presenilin-1 (APP+PS1) APP PS1 transgenic mouse is a model for amyloid deposition and as in AD the mice develop memory deficits
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.6	and as in AD the mice develop memory deficits and amyloid deposits accumulate
5438	IFNG	interferon, gamma	IFN-gamma	0.8	uninfected microglia exposed to inflammatory stimuli such as lipopolysaccharide and IFN-gamma as well as prion protein (PrP) PrP amyloid 5
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.6	lipopolysaccharide and IFN-gamma as well as prion protein (PrP) PrP amyloid 5
936	BAD	BCL2-antagonist of cell death	BAD	0.3	specific apoptosis-related gene candidates such as Bcl-xl and the calcineurin-mediated BAD dephosphorylation which is known to activate the caspase 3 apoptotic
445	SETX	senataxin	ALS4	1.0	the locus on 16q 1 91 and 93 and the ALS4 locus (9q34) 9q34 for early onset dominant ALS cases 10
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	Cystatin B was also found to be close to the SOD1 gene on chromosome 21
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	Time-dependent differential gene expression in spinal cord from the G93A SOD1 gene transgenic mouse model
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	6.9	spinal cord of animal model of the disease (G93A G93A SOD1 gene transgenic mouse candidate genes found to have an early
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	the first als locus als1 to be identified on chromosome 21 contains the cytosolic copper_amp_#x2013;zinc superoxide dismutase sod1 gene which has been found to harbour at least 100 different genetic mutations which account for up to 20% of fals cases [ 18 90 and 98 ].
7634	NAIP	NLR family, apoptosis inhibitory protein	neuronal apoptosis inhibitory protein	1.0	clusive data have emerged from the analysis of potential risk factors in als such as the neurofilament heavy subunit [ 25 ] the apolipoprotein e allele 4 [ 71 ] the gene survival motor neuron smn and neuronal apoptosis inhibitory protein naip [ 79 ].
613	APOE	apolipoprotein E	apolipoprotein e	1.0	no conclusive data have emerged from the analysis of potential risk factors in als such as the neurofilament heavy subunit [ 25 ] the apolipoprotein e allele 4 [ 71 ] the gene survival motor neuron smn and neuronal apoptosis inhibitory protein naip [ 79 ].
2169	CNTF	ciliary neurotrophic factor	ciliary neurotrophic factor	1.0	recently ciliary neurotrophic factor cntf has been proposed as a modifier gene since the rare null mutations cause an earlier age of onset of disease in fals cases carrying a sod1 mutation.
10940	SLC1A2	solute carrier family 1 (glial high affinity glutamate transporter), member 2	excitatory amino acid transporter 2	1.0	for this reason the expression of glutamate receptors and of the excitatory amino acid transporter 2 eaat2 which is involved in the removal of glutamate from the synapse in spinal cord have been extensively investigated [ 92 and 107 ].
6664	LOX	lysyl oxidase	lysyl oxidase	1.0	these _amp_#x201c;inducible_amp_#x201d; elements by virtue of their responsiveness to a wide range of cell _amp_#x201c;injury_amp_#x201d; events include thioredoxin lysyl oxidase lo flavin containing monooxygenase fmo1 interleukin i receptor accessory protein il 1racp and a transcript representing a possible 14 3 3 spinal cord isoform [ 59 and 60 ].
5995	IL1RAP	interleukin 1 receptor accessory protein	il 1racp	1.0	f their responsiveness to a wide range of cell _amp_#x201c;injury_amp_#x201d; events include thioredoxin lysyl oxidase lo flavin containing monooxygenase fmo1 interleukin i receptor accessory protein il 1racp and a transcript representing a possible 14 3 3 spinal cord isoform [ 59 and 60 ].
12435	TXN	thioredoxin	thioredoxin	1.0	these _amp_#x201c;inducible_amp_#x201d; elements by virtue of their responsiveness to a wide range of cell _amp_#x201c;injury_amp_#x201d; events include thioredoxin lysyl oxidase lo flavin containing monooxygenase fmo1 interleukin i receptor accessory protein il 1racp and a transcript representing a possible 14 3 3 spinal cord isoform [ 59 and 60 ].
12435	TXN	thioredoxin	thioredoxin	1.0	thioredoxin lo and fmo exert a powerful antioxidant function counteracting the copper catalysed oxidation of proteins in als tissue.
12435	TXN	thioredoxin	thioredoxin	1.0	thioredoxin has been previously reported to be remarkably over expressed in adult rat motor neurones following hypoglossal nerve axotomy [ 61 ] and to be strongly induced in erythrocytes from patients with famil
3238	EGR1	early growth response 1	zif 268	1.0	c jun and zif 268 two immediate early genes factors widely considered as markers of neuronal response to injury and apoptotic cell death have been found to be markedly increased in dorsal and ventral horns of autopsie
6204	JUN	jun oncogene	c jun	1.0	c jun and zif 268 two immediate early genes factors widely considered as markers of neuronal response to injury and apoptotic cell death have been found to be markedly increased in dorsal and ventral horns
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	nf kappa b	1.0	immunohistochemical expression of a number of gene candidates including c jun jnk/sapk a kinase that exerts a stress related activation of c jun and nf kappa b a transcription factor induced by oxidative injury with a prominent neuroprotective function have been assayed in different disease targeted tissues.
6204	JUN	jun oncogene	c jun	1.0	immunohistochemical expression of a number of gene candidates including c jun jnk/sapk a kinase that exerts a stress related activation of c jun and nf kappa b a transcription factor induced by oxidative injury with a prominent neuroprotective function have been assayed in different disease targeted tissues.
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	nf kappa b	1.0	the jnk/sapk c jun pathway was found to be markedly up regulated [ 67 ] in als spinal cord astrocytes together with nf kappa b whereas motor neurones show a lower expression of these molecules.
6204	JUN	jun oncogene	c jun	1.0	the jnk/sapk c jun pathway was found to be markedly up regulated [ 67 ] in als spinal cord astrocytes together with nf kappa b whereas motor neurones show a lower expression of these molecules.
2482	CSTB	cystatin B (stefin B)	cystatin b	1.0	another up regulated gene candidate was found to have a high homology with stefin b [stfb also called cystatin b cstb ] which is a member of the superfamily of non caspase cysteine protease inhibitors known to have an anti apoptotic function [ 45 and 85 ].
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	cysteine protease	1.0	another up regulated gene candidate was found to have a high homology with stefin b [stfb also called cystatin b cstb ] which is a member of the superfamily of non caspase cysteine protease inhibitors known to have an anti apoptotic function [ 45 and 85 ].
2482	CSTB	cystatin B (stefin B)	stefin b	1.0	another up regulated gene candidate was found to have a high homology with stefin b [stfb also called cystatin b cstb ] which is a member of the superfamily of non caspase cysteine protease inhibitors known to have an anti apoptotic function [ 45 and 85 ].
2482	CSTB	cystatin B (stefin B)	cystatin b	1.0	the majority of cases of progressive myoclonus epilepsy of the unverricht_amp_#x2013;lundborg type epm1 are caused by mutations mostly an expansion of a 12 bp polymorphic tandem repeat of the cystatin b gene [ 86 and 87 ].
2482	CSTB	cystatin B (stefin B)	cystatin b	1.0	these mutations are responsible for the cystatin b mrna down regulation in various tissues from patients with epm1 [ 49 ].
2482	CSTB	cystatin B (stefin B)	cystatin b	1.0	mice lacking cystatin b develop symptoms seen in the human disease with loss of cerebellar granule cells and other cellular changes characteristic of apoptosis [ 87 ].
2170	CNTFR	ciliary neurotrophic factor receptor	cntfr alpha	1.0	however genotyping of the cntf receptor alpha cntfr alpha has failed to show any significant association between allelic variants of this gene and familial als fals [ 44 ].
2170	CNTFR	ciliary neurotrophic factor receptor	cntfr alpha	1.0	a marked increase in cntfr alpha mrna expression was found in als spinal cord whereas the same transcript showed little or no expression in als motor cortex with no differences seen between als and control tissues [ 22 ].
4140	GAP43	growth associated protein 43	growth associated protein 43	1.0	the same pattern of up regulation in motor neurones from als spinal cord applies to growth associated protein 43 gap43 a phosphoprotein which is expressed during neurite elongation [ 42 ].
644	AR	androgen receptor (dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease)	androgen receptor	1.0	the presence of a known mutation in the androgen receptor creates a state of partial androgen insensitivity which is an important hallmark of the disease.
4601	GRN	granulin	granulin	1.0	granulin was found to be over expressed in spinal cord tissues from als individuals.
4601	GRN	granulin	granulin	1.0	previous studies on epithelin/granulin expression have identified a significant androgen related over expression in specific brain regions e.g hypothalamus of neonatal male rats as well as an oestradiol responsiveness in human breast canc
14922	HRASLS	HRAS-like suppressor	h rev107	1.0	another hormone sensitive transcript with high homology to rat h rev107 like protein was found to be significantly up regulated in als spinal cord.
9919	RBP1	retinol binding protein 1, cellular	retinol binding protein1	1.0	cellular retinol binding protein1 crbp1 showed a marked up regulation in als spinal cord [ 60 ].
2348	CREBBP	CREB binding protein (Rubinstein-Taybi syndrome)	creb binding protein	1.0	the hypothesis of an involvement of these molecular pathways in the pathogenesis of als may find some support in the study by yoshihara et al. [ 115 ] which shows a significant up regulation of a creb binding protein in the g93a transgenic tg animal model.
4601	GRN	granulin	granulin	1.0	in addition the over expression of hormone sensitive transcripts in als spinal cord such as granulin may be related to the presence of an abnormal sensitivity of particular regions of the spinal cord to the action of circulating hormones.
10618	CCL2	chemokine (C-C motif) ligand 2	mcp 1	1.0	in alzheimer's disease ad for example amyloid beta a beta deposition activates astrocytes and oligodendrocytes to produce chemokines mcp 1 and rantes which act as potent in vitro microglial and macrophage chemoattractants [ 46 ].
1774	CDK5	cyclin-dependent kinase 5	cyclin dependent kinase 5	1.0	c1qb clusterin apoj and the t cell receptor tcr transcript have been found to be markedly up regulated in areas of als spinal cord undergoing degeneration [ 30 and 80 ] whereas a study of cyclin dependent kinase 5 cdk 5 regional expression identified a significant up regulation in als affected motor neurones [ 6 ].
2095	CLU	clusterin	clusterin	1.0	c1qb clusterin apoj and the t cell receptor tcr transcript have been found to be markedly up regulated in areas of als spinal cord undergoing degeneration [ 30 and 80 ] whereas a study of cyclin dependent kinase 5
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	cox 2	1.0	cox 2 and cd11b a specific marker of microglia activation have been reported to be up regulated in als spinal cord tissue [ 113 ].
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	cox 2	1.0	the significant up regulation of cox 2 in als spinal cord compared to control tissues including patients affected by parkinson's disease pd ad cerebrovascular accidents and other non neurological disorders adds further evidence to the obs
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	cox 2	1.0	cox 2 mrna up regulation was restricted to pathologically affected tissue and this was accompanied by increased cox 2 protein levels.
5992	IL1B	interleukin 1, beta	il 1	1.0	ceptor accessory protein il 1racp mrna markedly over expressed in als spinal cord is a trans membrane protein belonging to a receptor complex which binds to the pro inflammatory protein interleukin 1 il 1 [ 14 ].
5995	IL1RAP	interleukin 1 receptor accessory protein	il 1racp	1.0	interleukin i receptor accessory protein il 1racp mrna markedly over expressed in als spinal cord is a trans membrane protein belonging to a receptor complex which binds to the pro inflammatory protein interleukin 1 il 1 [ 14 ].
5991	IL1A	interleukin 1, alpha	interleukin 1	1.0	terleukin i receptor accessory protein il 1racp mrna markedly over expressed in als spinal cord is a trans membrane protein belonging to a receptor complex which binds to the pro inflammatory protein interleukin 1 il 1 [ 14 ].
5995	IL1RAP	interleukin 1 receptor accessory protein	il 1racp	1.0	il 1racp has also been found to be up regulated in spinal cord from sod1 g93a transgenic mice [ 76 ].
6011	IL3	interleukin 3 (colony-stimulating factor, multiple)	interleukin 3	1.0	chavany et al. [ 11 ] reported that transgenic mice over expressing interleukin 3 develop a selective motor neurone degeneration with an auto immune reaction causing dendritic/axonal and somatic degeneration closely resembling als.
1907	CH25H	cholesterol 25-hydroxylase	cholesterol 25 hydroxylase	1.0	a consistent up regulation of cholesterol 25 hydroxylase has been identified in post mortem als spinal cord [ 60 ].
2641	CYP46A1	cytochrome P450, family 46, subfamily A, polypeptide 1	cholesterol 24 hydroxylase	1.0	a pivotal role for altered sphingolipid metabolism in neurodegeneration is also suggested by a recent study on cholesterol 24 hydroxylase encoded by the cyp46 gene.
6893	MAPT	microtubule-associated protein tau	tau protein	1.0	a cyp46 polymorphism is associated with an increased beta amyloid load in brain tissues increased cerebrospinal fluid levels of beta amyloid peptides/phosphorylated tau protein and to a higher risk of late onset sporadic ad [ 81 ].
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	towards the end stage of the disease bcl 2 and bcl xl proteins acting as apoptosis inhibitors show reduced expression whereas bad and bax which promote apoptosis appear to be up regulated in spinal cord of the animal model of als [ 109 ].
992	BCL2L1	BCL2-like 1	bcl xl	1.0	towards the end stage of the disease bcl 2 and bcl xl proteins acting as apoptosis inhibitors show reduced expression whereas bad and bax which promote apoptosis appear to be up regulated in spinal cord of the animal model of als [ 109 ].
12435	TXN	thioredoxin	thioredoxin	1.0	thioredoxin known to promote cell survival by suppressing caspase dependent apoptosis was found to be differentially regulated in a post mortem expression study of spinal cord from als cases in adult rat motor n
14922	HRASLS	HRAS-like suppressor	h rev107	1.0	other differentially expressed candidates in the post mortem study such as the human homologue of h rev107 like protein are known to have an intrinsic anti proliferative activity [ 41 ] or as in the case of the tal 1 proto oncogene to increase cell proliferation via an anti apoptotic effect.
11556	TAL1	T-cell acute lymphocytic leukemia 1	tal 1	1.0	rentially expressed candidates in the post mortem study such as the human homologue of h rev107 like protein are known to have an intrinsic anti proliferative activity [ 41 ] or as in the case of the tal 1 proto oncogene to increase cell proliferation via an anti apoptotic effect.
2482	CSTB	cystatin B (stefin B)	cystatin b	1.0	up regulation of cystatin b and 14 3 3 proteins in als spinal cord may also be seen as an anti apoptotic mechanism promoting cell survival.
613	APOE	apolipoprotein E	apolipoprotein e	1.0	apolipoprotein e apoe and to a lesser extent apo d gene expression are induced up to fivefold at 120 days of age.
4879	HEXB	hexosaminidase B (beta polypeptide)	hexosaminidase b	1.0	these include hexosaminidase b and brain fatty acid binding protein b fabp the latter acting as a molecular scavenger binding to oxidized fatty acids produced by lipid peroxidation.
3562	FABP7	fatty acid binding protein 7, brain	b fabp	1.0	these include hexosaminidase b and brain fatty acid binding protein b fabp the latter acting as a molecular scavenger binding to oxidized fatty acids produced by lipid peroxidation.
1907	CH25H	cholesterol 25-hydroxylase	cholesterol 25 hydroxylase	1.0	this seems to be in line with the end stage finding of increased expression of cholesterol 25 hydroxylase detected in the post mortem studies [ 60 ].
11881	TMSB4X	thymosin beta 4, X-linked	thymosin beta 4	1.0	among inflammatory candidates fig 4a transcripts for thymosin beta 4 a microglial marker are up regulated at 30 days whereas their expression declines at a later stage.
11881	TMSB4X	thymosin beta 4, X-linked	prothymosin beta 4	1.0	prothymosin beta 4 mrna undergoes a significant up regulation after 80 days of life.
9508	PSEN1	presenilin 1 (Alzheimer disease 3)	presenilin 1	1.0	the amyloid precursor protein/presenilin 1 app+ps1 transgenic mouse is a model for amyloid deposition and as in ad the mice develop memory deficits and amyloid deposits accumulate.
9449	PRNP	prion protein (p27-30) (Creutzfeldt-Jakob disease, Gerstmann-Strausler-Scheinker syndrome, fatal familial insomnia)	prion protein prp	1.0	inflammatory rna profile of microglia has been recently described which contrasts with that of uninfected microglia exposed to inflammatory stimuli such as lipopolysaccharide and ifn gamma as well as prion protein prp amyloid [ 5 ].
992	BCL2L1	BCL2-like 1	bcl xl	1.0	in these studies apoptotic or necrotic cell death was assessed through morphological criteria and gene expression analysis of specific apoptosis related gene candidates such as bcl xl and the calcineurin mediated bad dephosphorylation which is known to activate the caspase 3 apoptotic cascade [ 103 ].
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	ough morphological criteria and gene expression analysis of specific apoptosis related gene candidates such as bcl xl and the calcineurin mediated bad dephosphorylation which is known to activate the caspase 3 apoptotic cascade [ 103 ].
2482	CSTB	cystatin B (stefin B)	cystatin b	1.0	cystatin b was also found to be close to the sod1 gene on chromosome 21.
2482	CSTB	cystatin B (stefin B)	cystatin b	1.0	an tissue show the activation of unique neuroprotective mechanisms which are not identified in the studies of animal models exemplified by the up regulation of transcripts like 14 3 3 protein fmo and cystatin b. further insight in these changes which may be particularly relevant for the human form of the disease may open the way to a full understanding of the intrinsic molecular dysfunction leading to motor