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PMID	16510725 ( )
Title	Thalidomide and lenalidomide extend survival in a transgenic mouse model of amyotrophic lateral sclerosis.
Abstract	Accumulating evidence suggests that inflammation plays a major role in the pathogenesis of motor neuron death in amyotrophic lateral sclerosis (ALS). Important mediators of inflammation such as the cytokine tumor necrosis factor-alpha (TNF-alpha) and its superfamily member fibroblast-associated cell-surface ligand (FasL) have been implicated in apoptosis. We found increased TNF-alpha and FasL immunoreactivity in lumbar spinal cord sections of ALS patients and G93A transgenic mice. Both increased TNF-alpha and FasL immunostaining in the lumbar spinal cord of the G93A SOD1 transgenic mice occurred at 40-60 d, well before the onset of symptoms and loss of motor neurons. We tested the neuroprotective effect of thalidomide and its analog lenalidomide, pharmacological agents that inhibit the expression of TNF-alpha and other cytokines by destabilizing their mRNA. Treatment with either thalidomide or lenalidomide attenuated weight loss, enhanced motor performance, decreased motor neuron cell death, and significantly increased the life span in G93A transgenic mice. Treated G93A mice showed a reduction in TNF-alpha and FasL immunoreactivity as well as their mRNA in the lumbar spinal cord. Both compounds also reduced interleukin (IL)-12p40, IL-1alpha, and IL-1beta and increased IL-RA and TGF-beta1 mRNA. Therefore, both thalidomide and lenalidomide bear promise as therapeutic interventions for the treatment of ALS. University, New York-Presbyterian Hospital, New York, New York 10021, USA. mak2026@med.cornell.edu Neuroscience

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
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	138	tumor necrosis factor alpha \| TNF-alpha. \| TNF-alpha- \| tnf alpha \|
11936	FASLG	Fas ligand (TNF superfamily, member 6)	46	FasL-immunoreactive \|
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	30	SOD1 \| hSOD1 \| superoxide dismutase \|
5992	IL1B	interleukin 1, beta	18	IL-1 \| il 1 \|
4235	GFAP	glial fibrillary acidic protein	13	GFAP \|
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	10	caspase 8 \| caspase-8 \|
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	10	GAPDH \| glyceraldehyde 3 phosphate dehydrogenase \|
11920	FAS	Fas (TNF receptor superfamily, member 6)	5	CD95 \| Fas \| Fas-associated \|
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	4	TNF-R1 \| p55 \|
5993	IL1R1	interleukin 1 receptor, type I	4	IL-1RA \|
3573	FADD	Fas (TNFRSF6)-associated via death domain	3	FADD \|
11766	TGFB1	transforming growth factor, beta 1	3	TGF-beta1 \|
6018	IL6	interleukin 6 (interferon, beta 2)	2	IL-6 \| il 6 \|
11769	TGFB3	transforming growth factor, beta 3	2	tgf beta3 \| TGF-beta3 \|
5962	IL10	interleukin 10	2	IL-10 \| il 10 \|
5438	IFNG	interferon, gamma	2	IFN \|
5986	IL18	interleukin 18 (interferon-gamma-inducing factor)	2	il 18 \| IL-18 \|
12030	TRADD	TNFRSF1A-associated via death domain	1	TRADD \|
6876	MAPK14	mitogen-activated protein kinase 14	1	p38 \|
6024	IL7R	interleukin 7 receptor	1	IL-RA \|
7872	NOS1	nitric oxide synthase 1 (neuronal)	1	neuronal nitric oxide synthase \|
11917	TNFRSF1B	tumor necrosis factor receptor superfamily, member 1B	1	TNF-R2 \|
11919	CD40	CD40 molecule, TNF receptor superfamily member 5	1	CD40 \|
2681	DAXX	death-associated protein 6	1	Daxx \|

Targets by SciMiner Full list

HUGO ID	Symbol	Name	ActualStr	Score	FlankingText
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	mediators of inflammation such as the cytokine tumor necrosis factor-alpha TNF-alpha and its superfamily member fibroblast-associated cell-surface ligand (FasL) FasL have
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	factor-alpha TNF-alpha and its superfamily member fibroblast-associated cell-surface ligand (FasL) FasL have been implicated in apoptosis
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	We found increased TNF-alpha and FasL immunoreactivity in lumbar spinal cord sections of ALS
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	We found increased TNF-alpha and FasL immunoreactivity in lumbar spinal cord sections of ALS patients and
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Both increased TNF-alpha and FasL immunostaining in the lumbar spinal cord of the
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	Both increased TNF-alpha and FasL immunostaining in the lumbar spinal cord of the G93A SOD1
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	FasL immunostaining in the lumbar spinal cord of the G93A SOD1 transgenic mice occurred at 40-60 d well before the onset
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	its analog lenalidomide pharmacological agents that inhibit the expression of TNF-alpha and other cytokines by destabilizing their mRNA
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Treated G93A mice showed a reduction in TNF-alpha and FasL immunoreactivity as well as their mRNA in the
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	Treated G93A mice showed a reduction in TNF-alpha and FasL immunoreactivity as well as their mRNA in the lumbar spinal
5992	IL1B	interleukin 1, beta	IL-1	1.3	Both compounds also reduced interleukin (IL)-12p40, IL -12p40 IL-1 alpha and IL-1 beta and increased IL-RA and TGF-beta1 mRNA
5992	IL1B	interleukin 1, beta	IL-1	1.3	compounds also reduced interleukin (IL)-12p40, IL -12p40 IL-1 alpha and IL-1 beta and increased IL-RA and TGF-beta1 mRNA
6024	IL7R	interleukin 7 receptor	IL-RA	0.3	(IL)-12p40, IL -12p40 IL-1 alpha and IL-1 beta and increased IL-RA and TGF-beta1 mRNA
11766	TGFB1	transforming growth factor, beta 1	TGF-beta1	0.1	-12p40 IL-1 alpha and IL-1 beta and increased IL-RA and TGF-beta1 mRNA
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	Key words G93A SOD1 thalidomide lenalidomide TNF-alpha FasL
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Key words G93A SOD1 thalidomide lenalidomide TNF-alpha FasL
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	Key words G93A SOD1 thalidomide lenalidomide TNF-alpha FasL
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	of missense mutations in the enzyme copper-zinc superoxide dismutase (SOD1), SOD1 which is associated with 15-20% of familial ALS cases (Rosen
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Tumor necrosis factor-alpha TNF-alpha is a major inflammatory cytokine that elicits a wide range
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	TNF-R1	2.2	mediates its biological effects through activation of two distinct receptors TNF-R1 and TNF-R2 (Tartaglia Tartaglia and Goeddel 1992 alpha and its
11917	TNFRSF1B	tumor necrosis factor receptor superfamily, member 1B	TNF-R2	1.2	biological effects through activation of two distinct receptors TNF-R1 and TNF-R2 (Tartaglia Tartaglia and Goeddel 1992 alpha and its proapoptotic receptor
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	TNF-R1	2.2	(Tartaglia Tartaglia and Goeddel 1992 alpha and its proapoptotic receptor TNF-R1 mRNA are elevated at late presymptomatic stages of disease in
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF	1.7	G93A mice (Hensley Hensley et al. 2002 alpha and soluble TNF receptor are elevated in serum of humans with ALS (Poloni
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	Fibroblast-associated cell-surface ligand (FasL) FasL may play a critical role in the death of motor
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	role in the death of motor neurons associated with mutant SOD1 (Raoul Raoul et al. 2002 alpha can induce FasL (Pinkoski
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	mutant SOD1 (Raoul Raoul et al. 2002 alpha can induce FasL (Pinkoski Pinkoski et al. 2002 alpha binds to its receptor
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	TNF-R1	2.2	et al. 2002 alpha binds to its receptor (e.g., e.g. TNF-R1 similar to the events that take place when FasL binds
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	e.g. TNF-R1 similar to the events that take place when FasL binds to Fas then death-inducing signaling complex (DISC) DISC will
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.1	to the events that take place when FasL binds to Fas then death-inducing signaling complex (DISC) DISC will form and caspase-8
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase-8	2.0	Fas then death-inducing signaling complex (DISC) DISC will form and caspase-8 is activated which leads to apoptotic cell death
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	In the present study we examined the temporal pattern of TNF-alpha and FasL immunoreactivity in the lumbar spinal cord of G93A
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	present study we examined the temporal pattern of TNF-alpha and FasL immunoreactivity in the lumbar spinal cord of G93A mice
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Because previous work showed that the pro-inflammatroy cytokines TNF-alpha and FasL are elevated in both human and mouse models
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	Because previous work showed that the pro-inflammatroy cytokines TNF-alpha and FasL are elevated in both human and mouse models of ALS
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	effects of thalidomide and lenalidomide two immunomodulatory agents that inhibit TNF-alpha production (Corral Corral et al. 1999 Bartlett et al. 2004
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	G93A SOD1 transgenic familial ALS mice (high high copy number (Gurney Gurney
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	Six N1029 (wild-type wild-type SOD1 transgenic mice and six mice from the thalidomide- and vehicle-treated
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	The primers used were as follows TNF-alpha sense 5'-GACCCAGTGTGGGAAG-3' and antisense 5'-GGTTCAGTGATGT-AGCGA-3' glyceraldehyde-3-phosphate dehydrogenase (GAPDH), GAPDH sense
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	GAPDH	1.6	follows TNF-alpha sense 5'-GACCCAGTGTGGGAAG-3' and antisense 5'-GGTTCAGTGATGT-AGCGA-3' glyceraldehyde-3-phosphate dehydrogenase (GAPDH), GAPDH sense 5'-CCATGGAGAAGGCTGGG-3' and antisense 5'-CAAAA-GTTGTCATGGATGACC-3'
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	The amounts of TNF-alpha and GAPDH cDNA were calculated using linear regression analysis from
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	GAPDH	1.6	The amounts of TNF-alpha and GAPDH cDNA were calculated using linear regression analysis from standard curves
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	calculated using linear regression analysis from standard curves for both TNF-alpha and GAPDH and the amount of TNF-alpha cDNA was expressed
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	GAPDH	1.6	linear regression analysis from standard curves for both TNF-alpha and GAPDH and the amount of TNF-alpha cDNA was expressed as a
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	curves for both TNF-alpha and GAPDH and the amount of TNF-alpha cDNA was expressed as a percentage of GAPDH
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	GAPDH	1.6	amount of TNF-alpha cDNA was expressed as a percentage of GAPDH
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	The sections were immunostained with antibodies to TNF-alpha (Serotec, Serotec Raleigh NC FasL (Santa Santa Cruz Biotechnology Santa
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	were immunostained with antibodies to TNF-alpha (Serotec, Serotec Raleigh NC FasL (Santa Santa Cruz Biotechnology Santa Cruz CA CD40 (Serotec, Serotec
11919	CD40	CD40 molecule, TNF receptor superfamily member 5	CD40	0.6	Raleigh NC FasL (Santa Santa Cruz Biotechnology Santa Cruz CA CD40 (Serotec, Serotec Oxford UK and glial fibrillary acid protein (GFAP;
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	(Serotec, Serotec Oxford UK and glial fibrillary acid protein (GFAP; GFAP Dako Carpinteria CA using a modified avidin-biotin peroxidase technique
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Double immunofluorescence was performed to demonstrate the glial localization of TNF-alpha and FasL
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	was performed to demonstrate the glial localization of TNF-alpha and FasL
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	of the ALS patients had an I113T mutation of the SOD1 gene
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	sections (7 7 microm thick were prepared and processed for TNF-alpha or FasL immunohistochemistry as described above
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	7 microm thick were prepared and processed for TNF-alpha or FasL immunohistochemistry as described above
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha and FasL immunoreactivity in G93A SOD1 mouse model of ALS
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	TNF-alpha and FasL immunoreactivity in G93A SOD1 mouse model of ALS
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	TNF-alpha and FasL immunoreactivity in G93A SOD1 mouse model of ALS
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	We investigated the temporal pattern of TNF-alpha and FasL immunoreactivity in G93A SOD1 mice at 40 and
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	We investigated the temporal pattern of TNF-alpha and FasL immunoreactivity in G93A SOD1 mice at 40 and 60 d
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	the temporal pattern of TNF-alpha and FasL immunoreactivity in G93A SOD1 mice at 40 and 60 d (asymptomatic), asymptomatic 90 d
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Immunohistochemical analysis showed little TNF-alpha immunoreactivity at 40 d which appeared similar to controls in
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	from G93A mice with a healthy appearance were stained with TNF-alpha moderately and immunoreactivity became more intense at 90 and 110
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha colocalized with the motor neuron marker (SMI-32) SMI-32 (Kiaei Kiaei
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	of age as demonstrated by colocalization with the astrocyte marker GFAP by double immunofluorescence ( Fig 1
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha and FasL are important mediators of inflammation and they play
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	TNF-alpha and FasL are important mediators of inflammation and they play a role
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha.	1.7	models of ALS and patients with ALS show increases in TNF-alpha.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	In ALS patients antigenic TNF-alpha and its soluble receptors measured by ELISA were significantly higher
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas-associated	2.1	receptors was also present A study using RPAs showed increased Fas-associated death domain (FADD) FADD and TNF-alpha receptor p55 at 80
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	0.9	A study using RPAs showed increased Fas-associated death domain (FADD) FADD and TNF-alpha receptor p55 at 80 d which increased further
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	using RPAs showed increased Fas-associated death domain (FADD) FADD and TNF-alpha receptor p55 at 80 d which increased further at 120
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	p55	1.7	showed increased Fas-associated death domain (FADD) FADD and TNF-alpha receptor p55 at 80 d which increased further at 120 d in
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	alpha was increased in the lumbar spinal cord of G37R SOD1 mice at 7 and 10 months of age and the
5992	IL1B	interleukin 1, beta	IL-1	1.3	age and the signal was unchanged in the absence of IL-1 beta (Nguyen Nguyen et al. 2001 alpha expression at 11
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	expression at 11 weeks of age (5.3-fold) 5.3-fold in G93A SOD1 mice which increased further at 14 and 17 weeks (8-fold)
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Glial cells are the major source of TNF-alpha expression in the CNS
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	both lumbar spinal cord motor neurons and glia from G93A SOD1 mice express high levels of TNF-alpha and this occurs at
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	and glia from G93A SOD1 mice express high levels of TNF-alpha and this occurs at 60 d well before the onset
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	An increase in TNF-alpha mRNA was confirmed by real-time RT-PCR in G93A mice at
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Double labeling of TNF-alpha with GFAP confirmed expression of TNF-alpha in astrocytes ( Fig
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	Double labeling of TNF-alpha with GFAP confirmed expression of TNF-alpha in astrocytes ( Fig 1
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Double labeling of TNF-alpha with GFAP confirmed expression of TNF-alpha in astrocytes ( Fig 1
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	This is consistent with a previous study in which TNF-alpha immunoreactivity was increased at 17 weeks of age in microglia
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	weeks of age in microglia and motor neurons of G93A SOD1 mice (Yoshihara Yoshihara et al. 2002
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.1	Fas triggers cell death in embryonic motoneurons by a pathway requiring
6876	MAPK14	mitogen-activated protein kinase 14	p38	0.3	oxide synthase and involving Daxx apoptosis signal-regulated kinase 1 and p38 as well as the FADD/caspase-8 FADD caspase-8 pathway (Raoul Raoul
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	0.9	signal-regulated kinase 1 and p38 as well as the FADD/caspase-8 FADD caspase-8 pathway (Raoul Raoul et al. 2002 alpha upregulates FasL
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase-8	2.0	kinase 1 and p38 as well as the FADD/caspase-8 FADD caspase-8 pathway (Raoul Raoul et al. 2002 alpha upregulates FasL (Pinkoski
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	FADD caspase-8 pathway (Raoul Raoul et al. 2002 alpha upregulates FasL (Pinkoski Pinkoski et al. 2002 alpha immunostaining was found in
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	was found in the neurons of adjacent sections suggesting that FasL and TNF-alpha are coexpressed in these neurons ( Fig 3
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	in the neurons of adjacent sections suggesting that FasL and TNF-alpha are coexpressed in these neurons ( Fig 3
2681	DAXX	death-associated protein 6	Daxx	0.0	pathway requiring upregulation of neuronal nitric oxide synthase and involving Daxx apoptosis signal-regulated kinase 1 and p38 as well as the
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Because both TNF-alpha and FasL immunostaining were increased in G93A mice we examined
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	Because both TNF-alpha and FasL immunostaining were increased in G93A mice we examined the effects
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	thalidomide and its analog lenalidomide which inhibits the stability of TNF-alpha mRNA (Moreira Moreira et al. 1993 alpha and FasL expression
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	of TNF-alpha mRNA (Moreira Moreira et al. 1993 alpha and FasL expression in motor neurons of G93A mice There was a
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	onset and a significant attenuation of disease progression in G93A SOD1 mice ( Figs 4 -6
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Quantitative RT-PCR showed that both thalidomide and lenalidomide significantly reduced TNF-alpha mRNA levels at 110 d of age
5992	IL1B	interleukin 1, beta	IL-1	1.3	Both compounds also inhibited IL-12p40 IL-1 alpha and IL-1 beta
5992	IL1B	interleukin 1, beta	IL-1	1.3	Both compounds also inhibited IL-12p40 IL-1 alpha and IL-1 beta
5993	IL1R1	interleukin 1 receptor, type I	IL-1RA	0.3	IL-1RA and TGF-beta1 mRNA were upregulated in G93A mice treated with
11766	TGFB1	transforming growth factor, beta 1	TGF-beta1	0.1	IL-1RA and TGF-beta1 mRNA were upregulated in G93A mice treated with thalidomide and
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	a role of pro-inflammatory cytokines in ALS and suggest that TNF-alpha and FasL and related cytokines have important triggering roles in
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	of pro-inflammatory cytokines in ALS and suggest that TNF-alpha and FasL and related cytokines have important triggering roles in the pathogenesis
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha binds to TNF receptor-1 and activates it to ligate with
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF	1.7	TNF-alpha binds to TNF receptor-1 and activates it to ligate with TNF-alpha receptor-associated death
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	binds to TNF receptor-1 and activates it to ligate with TNF-alpha receptor-associated death domain (TRADD), TRADD forming the DISC that leads
12030	TRADD	TNFRSF1A-associated via death domain	TRADD	0.6	activates it to ligate with TNF-alpha receptor-associated death domain (TRADD), TRADD forming the DISC that leads to activation of caspase-8 resulting
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase-8	2.0	(TRADD), TRADD forming the DISC that leads to activation of caspase-8 resulting in Bid cleavage and the activation of executioner caspases-3
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	FasL works in a similar way by binding to Fas/CD95 Fas
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.1	FasL works in a similar way by binding to Fas/CD95 Fas CD95 receptor and activate it to cause FADD ligation and
11920	FAS	Fas (TNF receptor superfamily, member 6)	CD95	2.1	works in a similar way by binding to Fas/CD95 Fas CD95 receptor and activate it to cause FADD ligation and DISC
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	0.9	to Fas/CD95 Fas CD95 receptor and activate it to cause FADD ligation and DISC formation which also leads on to caspase-8
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase-8	2.0	FADD ligation and DISC formation which also leads on to caspase-8 activation Bid cleavage and ultimately activation of caspases-3 -6 and
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase-8	2.0	Because these two pathways converge on caspase-8 activation they may have synergistic effects
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Lenalidomide inhibited TNF-alpha with less potency compared with thalidomide in contrast lenalidomide was
5992	IL1B	interleukin 1, beta	IL-1	1.3	was more potent in inhibiting other cytokines such as IL-12p40 IL-1 alpha and IL-1 beta
5992	IL1B	interleukin 1, beta	IL-1	1.3	in inhibiting other cytokines such as IL-12p40 IL-1 alpha and IL-1 beta
5993	IL1R1	interleukin 1 receptor, type I	IL-1RA	0.3	and lenalidomide are able to upregulate anti-inflammatory cytokines such as IL-1RA and TGF-beta1 which may have neuroprotective effects
11766	TGFB1	transforming growth factor, beta 1	TGF-beta1	0.1	are able to upregulate anti-inflammatory cytokines such as IL-1RA and TGF-beta1 which may have neuroprotective effects
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	In both erythema nodosum leprosum and myelodysplastic syndromes upregulation of TNF-alpha production is postulated to contribute to disease pathogenesis
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	The suppression of spinal cord TNF-alpha mRNA in our study by thalidomide and lenalidomide hence extension
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha immunoreactivity in G93A SOD1 and control mice
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	TNF-alpha immunoreactivity in G93A SOD1 and control mice
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha immunoreactivity was examined in the spinal cords of transgenic G93A
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	immunoreactivity was examined in the spinal cords of transgenic G93A SOD1 mice at 40 60 90 and 110 d of age
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	hSOD1	1.4	and 110 d of age and in 110-d-old transgenic wild-type hSOD1 (N1029) N1029 control mice
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha immunoreactivity is seen in the anterior horn motor neurons (arrows),
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Thalidomide treatment reduced TNF-alpha immunoreactivity (middle middle row left panel
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha double immunofluorescence with GFAP showed that TNF-alpha colocalizes with GFAP
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	TNF-alpha double immunofluorescence with GFAP showed that TNF-alpha colocalizes with GFAP in astrocytes
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha double immunofluorescence with GFAP showed that TNF-alpha colocalizes with GFAP in astrocytes
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	TNF-alpha double immunofluorescence with GFAP showed that TNF-alpha colocalizes with GFAP in astrocytes
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	The white arrowhead points to an astrocyte labeled with TNF-alpha (green) green and GFAP (red) red and colocalization of TNF-alpha
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	points to an astrocyte labeled with TNF-alpha (green) green and GFAP (red) red and colocalization of TNF-alpha and GFAP (yellow) yellow
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha (green) green and GFAP (red) red and colocalization of TNF-alpha and GFAP (yellow) yellow
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	green and GFAP (red) red and colocalization of TNF-alpha and GFAP (yellow) yellow
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	FasL immunoreactivity in G93A SOD1 and control mice
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	FasL immunoreactivity in G93A SOD1 and control mice
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	FasL immunoreactivity in neurons of the ventral horn of the lumbar
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	Increases in FasL staining in neurons (arrowheads) arrowheads and neuronal processes occurred as
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	Thalidomide treatment reduced FasL immunoreactivity (middle middle row left panel
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	FasL double immunofluorescence with GFAP showed that FasL colocalizes with GFAP
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	FasL double immunofluorescence with GFAP showed that FasL colocalizes with GFAP in astrocytes
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	FasL double immunofluorescence with GFAP showed that FasL colocalizes with GFAP in astrocytes
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	FasL double immunofluorescence with GFAP showed that FasL colocalizes with GFAP in astrocytes
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	The white arrows point to astrocytes labeled with FasL (green) green and GFAP (red) red and colocalization of FasL
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	arrows point to astrocytes labeled with FasL (green) green and GFAP (red) red and colocalization of FasL and GFAP (yellow) yellow
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	FasL (green) green and GFAP (red) red and colocalization of FasL and GFAP (yellow) yellow
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	green and GFAP (red) red and colocalization of FasL and GFAP (yellow) yellow
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha and FasL immunoreactivity in human ALS and controls
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	TNF-alpha and FasL immunoreactivity in human ALS and controls
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	FasL (top top panels and TNF-alpha (bottom bottom panels immunoreactivities in
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	FasL (top top panels and TNF-alpha (bottom bottom panels immunoreactivities in the lumbar ventral horn of
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha-	1.7	We found TNF-alpha- and FasL-immunoreactive neurons in the lumbar spinal cord sections of
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL-immunoreactive	2.7	We found TNF-alpha- and FasL-immunoreactive neurons in the lumbar spinal cord sections of a familial
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	lumbar spinal cord sections of a familial ALS patient with SOD1 mutation (I113T) I113T and sporadic ALS patients
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Intense TNF-alpha and FasL immunoreactivity occurred predominantly in neurons of ALS patients
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	Intense TNF-alpha and FasL immunoreactivity occurred predominantly in neurons of ALS patients
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Coexistence of TNF-alpha and FasL occurred in the same neurons in adjacent sections
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	Coexistence of TNF-alpha and FasL occurred in the same neurons in adjacent sections of ALS
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	of thalidomide or lenalidomide treatment on motor performance in G93A SOD1 transgenic mice from 89 to 165 d of age
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	mg kg thalidomide 100 mg/kg mg kg lenalidomide vehicle-treated G93A SOD1
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	mg kg thalidomide 100 mg/kg mg kg lenalidomide vehicle-treated G93A SOD1
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	(Lenali) Lenali treatment on Nissl-stained neuronal cell counts in G93A SOD1 transgenic mice at 110 d of age
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Real-time RT-PCR for TNF-alpha expression in the spinal cord tissue of G93A SOD1 control
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	for TNF-alpha expression in the spinal cord tissue of G93A SOD1 control mice and G93A mice treated with thalidomide or lenalidomide
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	The amount of TNF-alpha cDNA was measured in the total cDNA made from total
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	cord tissue of 110-d-old N1029/B6SJL N1029 B6SJL controls and G93A SOD1 mice treated with vehicle thalidomide or lenalidomide
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha cDNA amount in different samples was normalized against GAPDH cDNA
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	GAPDH	1.6	TNF-alpha cDNA amount in different samples was normalized against GAPDH cDNA and expressed as a percentage of GAPDH cDNA (**
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	GAPDH	1.6	normalized against GAPDH cDNA and expressed as a percentage of GAPDH cDNA ( p _lt_ 0.01 *** p _lt_ 0.0005
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	GAPDH	1.6	There were no changes in GAPDH cDNA amount among the groups
5992	IL1B	interleukin 1, beta	IL-1	1.3	RNA was used against a RPA multiprobe of cytokines a IL-1 alpha RNA was elevated in vehicle-treated G93A mice compared with
5992	IL1B	interleukin 1, beta	IL-1	1.3	lenalidomide-treated G93A mice while unchanged in thalidomide-treated G93A mice b IL-1 beta RNA was elevated in vehicle-treated G93A mice compared with
5993	IL1R1	interleukin 1 receptor, type I	IL-1RA	0.3	significantly reduced in both lenalidomide- and thalidomide-treated G93A mice d IL-1RA RNA was elevated in vehicle-treated G93A mice compared with wild
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	GAPDH	1.6	RNA amounts in different samples were normalized against (L32 L32 GAPDH RNA multiplied by 1000 and presented as an arbitrary number
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	GAPDH	1.6	1000 and presented as an arbitrary number per (L32 L32 GAPDH RNA (* * p _lt_ 0.5 ** p _lt_ 0.05
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	Strong immunoreactivity for FasL was evident in neurons as early as 40 d
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	However FasL immunoreactivity was less pronounced at 110 d ( Fig 2
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Both TNF-alpha and FasL immunoreactivity persisted relatively strong in the lumbar spinal
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	Both TNF-alpha and FasL immunoreactivity persisted relatively strong in the lumbar spinal cord sections
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	We also examined the FasL immunoreactivity in astrocytes by double labeling with the astrocyte marker
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	immunoreactivity in astrocytes by double labeling with the astrocyte marker GFAP
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	FasL immunoreactivity colocalized with GFAP indicating that FasL immunostaining was found
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	FasL immunoreactivity colocalized with GFAP indicating that FasL immunostaining was found in both neurons and
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	FasL immunoreactivity colocalized with GFAP indicating that FasL immunostaining was found in both neurons and astrocytes similar to
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha.	1.7	immunostaining was found in both neurons and astrocytes similar to TNF-alpha.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha and FasL immunoreactivity in human ALS
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	TNF-alpha and FasL immunoreactivity in human ALS
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Consistent with the immunohistochemical findings in ALS transgenic mice intense TNF-alpha and FasL immunoreactivity occurred in the lumbar spinal cord sections
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	the immunohistochemical findings in ALS transgenic mice intense TNF-alpha and FasL immunoreactivity occurred in the lumbar spinal cord sections from an
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	lumbar spinal cord sections from an ALS patient with a SOD1 mutation (I113T) I113T as well as sporadic ALS patients whereas
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	ALS patients whereas control tissues showed very little or no TNF-alpha and FasL immunoreactivity ( Fig 3
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	whereas control tissues showed very little or no TNF-alpha and FasL immunoreactivity ( Fig 3
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha and FasL coexisted in the motor neurons
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	TNF-alpha and FasL coexisted in the motor neurons
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	in survival was associated with a marked dose-dependent decrease in TNF-alpha immunoreactivity in the motor neurons and glial cells in the
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	We show that thalidomide treatment reduced TNF-alpha and FasL immunoreactivity in the spinal cords of G93A mice
11936	FASLG	Fas ligand (TNF superfamily, member 6)	FasL	3.2	We show that thalidomide treatment reduced TNF-alpha and FasL immunoreactivity in the spinal cords of G93A mice ( Figs
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha mRNA in G93A mice
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	To determine whether TNF-alpha mRNA is upregulated and whether thalidomide and lenalidomide can block
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	from total RNA extracted from the spinal cords of G93A SOD1 mice treated with thalidomide or lenalidomide vehicle-treated G93A mice and
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	or lenalidomide vehicle-treated G93A mice and N1029 mice (wild-type wild-type SOD1 overexpressers at 110 d of age
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	TNF-alpha mRNA was increased 10-fold in G93A SOD1 mice compared with
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	TNF-alpha mRNA was increased 10-fold in G93A SOD1 mice compared with control littermates ( p _lt_ 0.005 (
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	1.7	Thalidomide and lenalidomide treatment reduced TNF-alpha mRNA significantly ( p _lt_ 0.01
5993	IL1R1	interleukin 1 receptor, type I	IL-1RA	0.3	lenalidomide downregulated interleukin (IL)-12p40 IL -12p40 and upregulated TGF-beta1 and IL-1RA in treated G93A mice compared with vehicle-treated G93A mice (
5992	IL1B	interleukin 1, beta	IL-1	1.3	Lenalidomide also downregulated IL-1 alpha and IL-1 beta
5992	IL1B	interleukin 1, beta	IL-1	1.3	Lenalidomide also downregulated IL-1 alpha and IL-1 beta
5962	IL10	interleukin 10	IL-10	1.3	No changes were detected in IL-12p35 IL-10 IL-18 IFN gamma or IFN beta IL-6 TGF-beta3 and LT
5986	IL18	interleukin 18 (interferon-gamma-inducing factor)	IL-18	1.3	No changes were detected in IL-12p35 IL-10 IL-18 IFN gamma or IFN beta IL-6 TGF-beta3 and LT alpha
5438	IFNG	interferon, gamma	IFN	0.3	No changes were detected in IL-12p35 IL-10 IL-18 IFN gamma or IFN beta IL-6 TGF-beta3 and LT alpha or
5438	IFNG	interferon, gamma	IFN	0.3	changes were detected in IL-12p35 IL-10 IL-18 IFN gamma or IFN beta IL-6 TGF-beta3 and LT alpha or LT beta (data
6018	IL6	interleukin 6 (interferon, beta 2)	IL-6	1.3	detected in IL-12p35 IL-10 IL-18 IFN gamma or IFN beta IL-6 TGF-beta3 and LT alpha or LT beta (data data not
11769	TGFB3	transforming growth factor, beta 3	TGF-beta3	0.2	in IL-12p35 IL-10 IL-18 IFN gamma or IFN beta IL-6 TGF-beta3 and LT alpha or LT beta (data data not shown
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	important mediators of inflammation such as the cytokine tumor necrosis factor alpha tnf alpha and its superfamily member fibroblast associated cell surface ligand fasl have been implicated in apoptosis.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tumor necrosis factor alpha	1.0	important mediators of inflammation such as the cytokine tumor necrosis factor alpha tnf alpha and its superfamily member fibroblast associated cell surface ligand fasl have been implicated in apoptosis.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we found increased tnf alpha and fasl immunoreactivity in lumbar spinal cord sections of als patients and g93a transgenic mice.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	both increased tnf alpha and fasl immunostaining in the lumbar spinal cord of the g93a sod1 transgenic mice occurred at 40 60 d well before the onset of symptoms and loss of motor neurons.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we tested the neuroprotective effect of thalidomide and its analog lenalidomide pharmacological agents that inhibit the expression of tnf alpha and other cytokines by destabilizing their mrna.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	treated g93a mice showed a reduction in tnf alpha and fasl immunoreactivity as well as their mrna in the lumbar spinal cord.
5992	IL1B	interleukin 1, beta	il 1	1.0	both compounds also reduced interleukin il 12p40 il 1 alpha and il 1 beta and increased il ra and tgf beta1 mrna.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	key words: g93a; sod1; thalidomide; lenalidomide; tnf alpha; fasl
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	a major discovery in the study of als was the finding of missense mutations in the enzyme copper zinc superoxide dismutase sod1 which is associated with 15 20% of familial als cases rosen et al. 1993 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tumor necrosis factor alpha tnf alpha is a major inflammatory cytokine that elicits a wide range of biological responses including neuronal apoptosis tewari and dixit 1996 alpha mediates its biological effects through activation of two d
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tumor necrosis factor alpha	1.0	tumor necrosis factor alpha tnf alpha is a major inflammatory cytokine that elicits a wide range of biological responses including neuronal apoptosis tewari and dixit 1996 alpha mediates its biological effects through activatio
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	lpha can induce fasl pinkoski et al. 2002 alpha binds to its receptor e.g. tnf r1 similar to the events that take place when fasl binds to fas then death inducing signaling complex disc will form and caspase 8 is activated which leads to apoptotic cell death.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	in the present study we examined the temporal pattern of tnf alpha and fasl immunoreactivity in the lumbar spinal cord of g93a mice.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	because previous work showed that the pro inflammatroy cytokines tnf alpha and fasl are elevated in both human and mouse models of als and play a role in the pathogenesis of als we tested the neuroprotective effects of thalidomide and lenalidomide two immunomodulatory agent
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	levated in both human and mouse models of als and play a role in the pathogenesis of als we tested the neuroprotective effects of thalidomide and lenalidomide two immunomodulatory agents that inhibit tnf alpha production corral et al. 1999 ; bartlett et al. 2004 .
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	glyceraldehyde 3 phosphate dehydrogenase	1.0	the primers used were as follows: tnf alpha sense 5' gacccagtgtgggaag 3' and antisense 5' ggttcagtgatgt agcga 3'; glyceraldehyde 3 phosphate dehydrogenase gapdh sense 5' ccatggagaaggctggg 3' and antisense 5' caaaa gttgtcatggatgacc 3'.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	the primers used were as follows: tnf alpha sense 5' gacccagtgtgggaag 3' and antisense 5' ggttcagtgatgt agcga 3'; glyceraldehyde 3 phosphate dehydrogenase gapdh sense 5' ccatggagaaggctggg 3' and antisense 5' caaaa gttgtcatggatgacc 3'.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	the amounts of tnf alpha and gapdh cdna were calculated using linear regression analysis from standard curves for both tnf alpha and gapdh and the amount of tnf alpha cdna was expressed as a percentage of gapdh.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	the sections were immunostained with antibodies to tnf alpha serotec raleigh nc fasl santa cruz biotechnology santa cruz ca cd40 serotec oxford uk and glial fibrillary acid protein gfap; dako carpinteria ca using a modified avidin biotin peroxidase technique.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	double immunofluorescence was performed to demonstrate the glial localization of tnf alpha and fasl.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	sections were incubated for 18 h in the primary antibody mixture containing anti tnf alpha or anti fasl and the astrocyte marker anti gfap.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	paraffin sections 7 microm thick were prepared and processed for tnf alpha or fasl immunohistochemistry as described above.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha and fasl immunoreactivity in g93a sod1 mouse model of als
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we investigated the temporal pattern of tnf alpha and fasl immunoreactivity in g93a sod1 mice at 40 and 60 d asymptomatic 90 d early symptomatic 110 d fully symptomatic and end stage 120 135 d in the ventral horn of the lumbar spinal cords.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	immunohistochemical analysis showed little tnf alpha immunoreactivity at 40 d which appeared similar to controls in the motor neurons of the ventral horn in the lumbar spinal cord.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	at 60 d motor neurons from g93a mice with a healthy appearance were stained with tnf alpha moderately and immunoreactivity became more intense at 90 and 110 d.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha colocalized with the motor neuron marker smi 32 kiaei et al. 2006 alpha staining also occurred in actrocytes at 110 d of age as demonstrated by colocalization with the astrocyte marker gfap by double
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha and fasl are important mediators of inflammation and they play a role in apoptosis.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	studies performed in mouse models of als and patients with als show increases in tnf alpha.
5992	IL1B	interleukin 1, beta	il 1	1.0	ther at 120 d in high expressing g93a mice hensley et al. 2002 alpha was increased in the lumbar spinal cord of g37r sod1 mice at 7 and 10 months of age and the signal was unchanged in the absence of il 1 beta nguyen et al. 2001 alpha expression at 11 weeks of age 5.3 fold in g93a sod1 mice which increased further at 14 and 17 weeks 8 fold yoshihara et al. 2002 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	in als patients antigenic tnf alpha and its soluble receptors measured by elisa were significantly higher in als patients than in healthy controls poloni et al. 2000 alpha mrna expression in spinal cords of g93a mice at 4 months of age
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	me weaker reaching a maximum at 7.5 8 months of age in low copy number g93a mice elliott 2001 alpha receptors was also present a study using rpas showed increased fas associated death domain fadd and tnf alpha receptor p55 at 80 d which increased further at 120 d in high expressing g93a mice hensley et al. 2002 alpha was increased in the lumbar spinal cord of g37r sod1 mice at 7 and 10 months of age and th
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	glial cells are the major source of tnf alpha expression in the cns.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we found that both lumbar spinal cord motor neurons and glia from g93a sod1 mice express high levels of tnf alpha and this occurs at 60 d well before the onset of symptoms.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	an increase in tnf alpha mrna was confirmed by real time rt pcr in g93a mice at 110 d.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	double labeling of tnf alpha with gfap confirmed expression of tnf alpha in astrocytes fig 1 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	this is consistent with a previous study in which tnf alpha immunoreactivity was increased at 17 weeks of age in microglia and motor neurons of g93a sod1 mice yoshihara et al. 2002 .
7872	NOS1	nitric oxide synthase 1 (neuronal)	neuronal nitric oxide synthase	1.0	fas triggers cell death in embryonic motoneurons by a pathway requiring upregulation of neuronal nitric oxide synthase and involving daxx apoptosis signal regulated kinase 1 and p38 as well as the fadd/caspase 8 pathway raoul et al. 2002 alpha upregulates fasl pinkoski et al. 2002 alpha immunostaining was found in th
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	and p38 as well as the fadd/caspase 8 pathway raoul et al. 2002 alpha upregulates fasl pinkoski et al. 2002 alpha immunostaining was found in the neurons of adjacent sections suggesting that fasl and tnf alpha are coexpressed in these neurons fig 3 .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	s triggers cell death in embryonic motoneurons by a pathway requiring upregulation of neuronal nitric oxide synthase and involving daxx apoptosis signal regulated kinase 1 and p38 as well as the fadd/caspase 8 pathway raoul et al. 2002 alpha upregulates fasl pinkoski et al. 2002 alpha immunostaining was found in the neurons of adjacent sections suggesting that fasl and tnf alpha are coexpressed in these ne
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	because both tnf alpha and fasl immunostaining were increased in g93a mice we examined the effects of thalidomide and its analog lenalidomide which inhibits the stability of tnf alpha mrna moreira et al. 1993 alpha and fasl expression in motor neurons of g93a mice there was a delay of disease onset and a significant attenuation of disease progression in g93a sod1 mice figs 4 6 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	quantitative rt pcr showed that both thalidomide and lenalidomide significantly reduced tnf alpha mrna levels at 110 d of age.
5992	IL1B	interleukin 1, beta	il 1	1.0	both compounds also inhibited il 12p40 il 1 alpha and il 1 beta.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	our findings provide additional evidence for a role of pro inflammatory cytokines in als and suggest that tnf alpha and fasl and related cytokines have important triggering roles in the pathogenesis of als in initiating a cell death pathway s .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha binds to tnf receptor 1 and activates it to ligate with tnf alpha receptor associated death domain tradd forming the disc that leads to activation of caspase 8 resulting in bid cleavage and the activation of executioner caspases 3 6 and 7.
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	tnf alpha binds to tnf receptor 1 and activates it to ligate with tnf alpha receptor associated death domain tradd forming the disc that leads to activation of caspase 8 resulting in bid cleavage and the activation of executioner caspases 3 6 and 7.
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	fasl works in a similar way by binding to fas/cd95 receptor and activate it to cause fadd ligation and disc formation which also leads on to caspase 8 activation bid cleavage and ultimately activation of caspases 3 6 and 7 nagata 1997 1999 ; pinkoski et al. 2000 ; ugolini et al. 2003 .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	because these two pathways converge on caspase 8 activation they may have synergistic effects.
5992	IL1B	interleukin 1, beta	il 1	1.0	lenalidomide inhibited tnf alpha with less potency compared with thalidomide; in contrast lenalidomide was more potent in inhibiting other cytokines such as il 12p40 il 1 alpha and il 1 beta.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	lenalidomide inhibited tnf alpha with less potency compared with thalidomide; in contrast lenalidomide was more potent in inhibiting other cytokines such as il 12p40 il 1 alpha and il 1 beta.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	in both erythema nodosum leprosum and myelodysplastic syndromes upregulation of tnf alpha production is postulated to contribute to disease pathogenesis.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	the suppression of spinal cord tnf alpha mrna in our study by thalidomide and lenalidomide hence extension of survival in g93a mice suggests that this class of immunomodulatory agents may have efficacy in diseases of the cns associated with
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha immunoreactivity in g93a sod1 and control mice.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha immunoreactivity was examined in the spinal cords of transgenic g93a sod1 mice at 40 60 90 and 110 d of age and in 110 d old transgenic wild type hsod1 n1029 control mice.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha immunoreactivity is seen in the anterior horn motor neurons arrows with heavy staining in the cytoplasm and nucleus of motor neurons.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	thalidomide treatment reduced tnf alpha immunoreactivity middle row left panel .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha double immunofluorescence with gfap showed that tnf alpha colocalizes with gfap in astrocytes.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	the white arrowhead points to an astrocyte labeled with tnf alpha green and gfap red and colocalization of tnf alpha and gfap yellow .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha and fasl immunoreactivity in human als and controls.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	fasl top panels and tnf alpha bottom panels immunoreactivities in the lumbar ventral horn of the spinal cord of human als and control patients.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we found tnf alpha and fasl immunoreactive neurons in the lumbar spinal cord sections of a familial als patient with sod1 mutation i113t and sporadic als patients.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	intense tnf alpha and fasl immunoreactivity occurred predominantly in neurons of als patients.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	coexistence of tnf alpha and fasl occurred in the same neurons in adjacent sections of als patients.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	real time rt pcr for tnf alpha expression in the spinal cord tissue of g93a sod1 control mice and g93a mice treated with thalidomide or lenalidomide.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	the amount of tnf alpha cdna was measured in the total cdna made from total mrna isolated from spinal cord tissue of 110 d old n1029/b6sjl controls and g93a sod1 mice treated with vehicle thalidomide or lenalidomide.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha cdna amount in different samples was normalized against gapdh cdna and expressed as a percentage of gapdh cdna p _lt_ 0.01; * p _lt_ 0.0005; mann whitney test .
5992	IL1B	interleukin 1, beta	il 1	1.0	spinal cord total rna was used against a rpa multiprobe of cytokines. a il 1 alpha rna was elevated in vehicle treated g93a mice compared with wild type n1020 controls and significantly reduced in lenalidomide treated g93a mice while unchanged in thalidomide treated g93a mice
5992	IL1B	interleukin 1, beta	il 1	1.0	ha rna was elevated in vehicle treated g93a mice compared with wild type n1020 controls and significantly reduced in lenalidomide treated g93a mice while unchanged in thalidomide treated g93a mice. b il 1 beta rna was elevated in vehicle treated g93a mice compared with wild type n1020 controls and significantly reduced by lenalidomide but not thalidomide treatment. c il 12p40 rna was elevated in vehic
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	both tnf alpha and fasl immunoreactivity persisted relatively strong in the lumbar spinal cord sections of g93a mice at end stage data not shown .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	fasl immunoreactivity colocalized with gfap indicating that fasl immunostaining was found in both neurons and astrocytes similar to tnf alpha.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha and fasl immunoreactivity in human als
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	consistent with the immunohistochemical findings in als transgenic mice intense tnf alpha and fasl immunoreactivity occurred in the lumbar spinal cord sections from an als patient with a sod1 mutation i113t as well as sporadic als patients whereas control tissues showed very little or no
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	and fasl immunoreactivity occurred in the lumbar spinal cord sections from an als patient with a sod1 mutation i113t as well as sporadic als patients whereas control tissues showed very little or no tnf alpha and fasl immunoreactivity fig 3 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha and fasl coexisted in the motor neurons.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	histological analysis revealed that the increase in survival was associated with a marked dose dependent decrease in tnf alpha immunoreactivity in the motor neurons and glial cells in the spinal cord lumbar regions of g93a mice compared with saline treated controls data not shown .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we show that thalidomide treatment reduced tnf alpha and fasl immunoreactivity in the spinal cords of g93a mice figs 1 2 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha mrna in g93a mice
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	to determine whether tnf alpha mrna is upregulated and whether thalidomide and lenalidomide can block its mrna elevation in the spinal cord of g93a mice real time quantitative pcr was performed using cdna synthesized from total rn
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha mrna was increased 10 fold in g93a sod1 mice compared with control littermates p _lt_ 0.005 fig 7 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	thalidomide and lenalidomide treatment reduced tnf alpha mrna significantly p _lt_ 0.01 .
5992	IL1B	interleukin 1, beta	il 1	1.0	lenalidomide also downregulated il 1 alpha and il 1 beta.
11769	TGFB3	transforming growth factor, beta 3	tgf beta3	1.0	no changes were detected in il 12p35 il 10 il 18 ifn gamma or ifn beta il 6 tgf beta3 and lt alpha or lt beta data not shown .
5962	IL10	interleukin 10	il 10	1.0	no changes were detected in il 12p35 il 10 il 18 ifn gamma or ifn beta il 6 tgf beta3 and lt alpha or lt beta data not shown .
5986	IL18	interleukin 18 (interferon-gamma-inducing factor)	il 18	1.0	no changes were detected in il 12p35 il 10 il 18 ifn gamma or ifn beta il 6 tgf beta3 and lt alpha or lt beta data not shown .
6018	IL6	interleukin 6 (interferon, beta 2)	il 6	1.0	no changes were detected in il 12p35 il 10 il 18 ifn gamma or ifn beta il 6 tgf beta3 and lt alpha or lt beta data not shown .