)| PMID |
17015226 ( ) |
|---|---|
| Title | ALS: a disease of motor neurons and their nonneuronal neighbors. |
| Abstract | Amyotrophic lateral sclerosis is a late-onset progressive neurodegenerative disease affecting motor neurons. The etiology of most ALS cases remains unknown, but 2% of instances are due to mutations in Cu/Zn superoxide dismutase (SOD1). Since sporadic and familial ALS affects the same neurons with similar pathology, it is hoped that therapies effective in mutant SOD1 models will translate to sporadic ALS. Mutant SOD1 induces non-cell-autonomous motor neuron killing by an unknown gain of toxicity. Selective vulnerability of motor neurons likely arises from a combination of several mechanisms, including protein misfolding, mitochondrial dysfunction, oxidative damage, defective axonal transport, excitotoxicity, insufficient growth factor signaling, and inflammation. Damage within motor neurons is enhanced by damage incurred by nonneuronal neighboring cells, via an inflammatory response that accelerates disease progression. These findings validate therapeutic approaches aimed at nonneuronal cells. Neuroscience, University of California, San Diego, La Jolla, California 92093, USA. |
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)) | 175 | superoxide dismutase 1 | SOD1 | ALS1 | SOD1- | SOD1-containing | hSOD1 | SOD1-mediated | SOD1-Mediated | mSOD1 | SOD1-expressing | |
| 12680 | VEGFA | vascular endothelial growth factor A | 20 | VEGF | vascular endothelial growth factor | |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | 15 | HSPs | HSP | hsp70 | Hsp70 | |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | 13 | nf l | NF-L | |
| 483 | ANG | angiogenin, ribonuclease, RNase A family, 5 | 12 | angiogenin | ANG | |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | 11 | GLT-1 | EAAT2 | glt 1 | |
| 12649 | VAPB | VAMP (vesicle-associated membrane protein)-associated protein B and C | 10 | ALS8 | VAPB | |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | 10 | Bcl-2 | bcl 2 | |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | 9 | insulin like growth factor 1 | IGF-1 | |
| 7734 | NEFM | neurofilament, medium polypeptide 150kDa | 6 | NF-M | nf m | |
| 7737 | NEFH | neurofilament, heavy polypeptide 200kDa | 6 | NF-H | |
| 1613 | CCS | copper chaperone for superoxide dismutase | 6 | CCS | |
| 5246 | HSPB1 | heat shock 27kDa protein 1 | 5 | Hsp25 | Hsp27 | |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | 5 | COX-2 | cox 2 | |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | 4 | Fas | Fas-ligand | |
| 4572 | GRIA2 | glutamate receptor, ionotropic, AMPA 2 | 4 | GluR2 | |
| 4232 | GDNF | glial cell derived neurotrophic factor | 4 | glial derived neurotrophic factor | GDNF | |
| 9461 | PRPH | peripherin | 3 | peripherin | |
| 1033 | BDNF | brain-derived neurotrophic factor | 3 | BDNF | |
| 10417 | RPS27A | ribosomal protein S27a | 2 | ubiquitin | |
| 2169 | CNTF | ciliary neurotrophic factor | 2 | CNTF | |
| 8982 | PIK3R4 | phosphoinositide-3-kinase, regulatory subunit 4 | 2 | p150 | |
| 11936 | FASLG | Fas ligand (TNF superfamily, member 6) | 2 | FasL | fas ligand | |
| 5253 | HSP90AA1 | heat shock protein 90kDa alpha (cytosolic), class A member 1 | 2 | Hsp90 | |
| 11917 | TNFRSF1B | tumor necrosis factor receptor superfamily, member 1B | 2 | p75 | NTR | |
| 4235 | GFAP | glial fibrillary acidic protein | 2 | glial fibrillary acidic protein | GFAP | |
| 5270 | DNAJB1 | DnaJ (Hsp40) homolog, subfamily B, member 1 | 2 | Hsp40 | |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | 2 | caspase 3 | |
| 2711 | DCTN1 | dynactin 1 (p150, glued homolog, Drosophila) | 2 | p150 glued | |
| 7808 | NGF | nerve growth factor (beta polypeptide) | 2 | NGF | |
| 7756 | NES | nestin | 1 | nestin | |
| 15869 | KIF16B | kinesin family member 16B | 1 | kinesin motor protein | |
| 4223 | MSTN | myostatin | 1 | myostatin | |
| 19986 | CYCS | cytochrome c, somatic | 1 | cytochrome c | |
| 12499 | UBE4A | ubiquitination factor E4A (UFD2 homolog, yeast) | 1 | UFD2 | |
| 9788 | RAB7A | RAB7A, member RAS oncogene family | 1 | Rab7 | |
| 11241 | SPI1 | spleen focus forming virus (SFFV) proviral integration oncogene spi1 | 1 | PU.1 | |
| 15860 | PRPF6 | PRP6 pre-mRNA processing factor 6 homolog (S. cerevisiae) | 1 | TOM | |
| 19349 | KIF21A | kinesin family member 21A | 1 | KIF21A | |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | 1 | CD11b | |
| 18652 | VPS54 | vacuolar protein sorting 54 homolog (S. cerevisiae) | 1 | Vps54 | |
| 6323 | KIF5A | kinesin family member 5A | 1 | KIF5A | |
| 727 | ARTN | artemin | 1 | neurotrophic factor | |
| 17877 | NMNAT1 | nicotinamide nucleotide adenylyltransferase 1 | 1 | Nmnat | |
| 6953 | CD46 | CD46 molecule, complement regulatory protein | 1 | MCP-1_amp_#x3b1 | |
| 13209 | ARHGEF5 | Rho guanine nucleotide exchange factor (GEF) 5 | 1 | TIM | |
| 1189 | AHSA1 | AHA1, activator of heat shock 90kDa protein ATPase homolog 1 (yeast) | 1 | p38 | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 1 | tumor necrosis factor | |
| 2681 | DAXX | death-associated protein 6 | 1 | Daxx | |
| 5224 | HSF1 | heat shock transcription factor 1 | 1 | HSF-1 | |
| 10647 | CX3CL1 | chemokine (C-X3-C motif) ligand 1 | 1 | fractalkine | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | ALS1 | 4.5 | motor neuron diseases ( Table 1 have been defined as ALS1 through ALS8 as well as ALS with frontotemporal dementia (ALS-FTD) |
| 12649 | VAPB | VAMP (vesicle-associated membrane protein)-associated protein B and C | ALS8 | 3.6 | diseases ( Table 1 have been defined as ALS1 through ALS8 as well as ALS with frontotemporal dementia (ALS-FTD) ALS-FTD and |
| 483 | ANG | angiogenin, ribonuclease, RNase A family, 5 | ANG | 0.6 | Mutations in genes encoding angiogenin ( ANG and VEGF and sequence variants in neurofilament genes have also |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Mutations in genes encoding angiogenin ( ANG and VEGF and sequence variants in neurofilament genes have also been reported |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | ALS1 | 4.5 | that affects motor neurons the nomenclature is misleading since only ALS1 ALS3 ALS6 ALS7 mutations in angiogenin and VEGF and a |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | since only ALS1 ALS3 ALS6 ALS7 mutations in angiogenin and VEGF and a small proportion of incidences of ALS8 represent the |
| 12649 | VAPB | VAMP (vesicle-associated membrane protein)-associated protein B and C | ALS8 | 3.6 | angiogenin and VEGF and a small proportion of incidences of ALS8 represent the classic late-onset neurodegenerative disease with selective killing of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | ALS1 | 4.5 | all of these disease incidences only the genes responsible for ALS1 ALS8 and ALS-FTDP have been identified |
| 12649 | VAPB | VAMP (vesicle-associated membrane protein)-associated protein B and C | ALS8 | 3.6 | of these disease incidences only the genes responsible for ALS1 ALS8 and ALS-FTDP have been identified |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | ALS1_amp_#x2014 Mutation in SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | ALS1 | 4.5 | The lion's share of work has focused on ALS1 caused by_amp_#xa0 mutations in Cu/Zn Cu Zn superoxide dismutase (SOD1) |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | caused by_amp_#xa0 mutations in Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Mutations in the SOD1 gene are the most common form of inherited ALS accounting |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Since the first SOD1 missense mutations were reported in 1993 ( Rosen et_amp_#xa0 al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | With the exception of a few instances all SOD1 mutations are dominant |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Sporadic and SOD1 mutant-mediated familial ALS are clinically indistinguishable and affect the same |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | The alanine-to-valine substitution at position 4 of SOD1 (SOD1 SOD1 A4V is the most prominent mutation in North |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | The alanine-to-valine substitution at position 4 of SOD1 (SOD1 SOD1 A4V is the most prominent mutation in North America responsible |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Mice and rats expressing mutant forms of human or mouse SOD1 develop progressive motor neuron degeneration ( Bruijn et_amp_#xa0 al. 1997 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Vascular Endothelial Growth Factor (VEGF) VEGF |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Vascular endothelial growth factor (VEGF), VEGF an established regulator of developmental hypoxia-induced and tumor-induced angiogenesis gained |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | of the hypoxia response element (HRE) HRE in the murine VEGF promoter resulted in ALS-like disease in mice ( Oosthuyse et_amp_#xa0 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF is widely expressed throughout the central nervous system (CNS) CNS |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Screening of ALS patient DNAs in promoter regions of the VEGF gene including the HRE and regions known to correlate with |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | the HRE and regions known to correlate with downregulation of VEGF synthesis found no link between HRE variants and disease ( |
| 483 | ANG | angiogenin, ribonuclease, RNase A family, 5 | ANG | 0.6 | Angiogenin ( ANG |
| 483 | ANG | angiogenin, ribonuclease, RNase A family, 5 | ANG | 0.6 | Mutations in ANG have also been linked to ALS emphasizing a potential link |
| 483 | ANG | angiogenin, ribonuclease, RNase A family, 5 | ANG | 0.6 | Swedish and North American populations and therefore suggest that ALS-linked ANG mutations are rare |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Whether angiogenin is endowed with neurotrophic properties like VEGF in addition to its angiogenic activity is not yet established |
| 12649 | VAPB | VAMP (vesicle-associated membrane protein)-associated protein B and C | VAPB | 4.2 | ALS8_amp_#x2014 VAMP-Associated Protein B (VAPB) VAPB |
| 12649 | VAPB | VAMP (vesicle-associated membrane protein)-associated protein B and C | VAPB | 4.2 | gene encoding v esicle-a ssociated membrane p rotein B ( VAPB also known as synaptobrevin-associated protein B VAPB has been implicated |
| 12649 | VAPB | VAMP (vesicle-associated membrane protein)-associated protein B and C | VAPB | 4.2 | rotein B ( VAPB also known as synaptobrevin-associated protein B VAPB has been implicated in endoplasmic reticulum to Golgi transport albeit |
| 12649 | VAPB | VAMP (vesicle-associated membrane protein)-associated protein B and C | VAPB | 4.2 | position 56 affects the functional properties of the ubiquitously expressed VAPB |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | 1984b and are also seen in ALS mice expressing mutant SOD1 ( Bruijn et_amp_#xa0 al. 1997 and Dal Canto and Gurney |
| 7737 | NEFH | neurofilament, heavy polypeptide 200kDa | NF-H | 0.9 | In addition mice with increased levels of wild-type NF-H or NF-L subunits develop age-dependent motor neuron pathology ( Cote |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | NF-L | 2.4 | In addition mice with increased levels of wild-type NF-H or NF-L subunits develop age-dependent motor neuron pathology ( Cote et_amp_#xa0 al. |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | NF-L | 2.4 | et_amp_#xa0 al. 1993 while expression of a point mutation in NF-L at levels corresponding to that expected for dominantly inherited disease |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | NF-L | 2.4 | ( Garcia et_amp_#xa0 al. 2006 although dominant point mutations in NF-L have been linked to a milder motor neuron disease Charcot-Marie-Tooth |
| 7737 | NEFH | neurofilament, heavy polypeptide 200kDa | NF-H | 0.9 | or 45 KSP repeats in the tail domain of the NF-H subunit have been reported in 1% of sporadic ALS patients |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | no affect on disease course in mice having an ALS-causing SOD1 mutation ( Lariviere et_amp_#xa0 al. 2003 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Motor Neuron Death from Toxicity of Mutant SOD1 Not Loss of Dismutase Activity |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | SOD1 is an abundant ubiquitously expressed cytosolic enzyme |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Since the known activity of SOD1 is to dismutate (or or convert superoxide a natural byproduct |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | However animals expressing dismutase active (hSOD1 hSOD1 G37R Wong et_amp_#xa0 al. 1995 and hSOD1 G93A Gurney et_amp_#xa0 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | dismutase active (hSOD1 hSOD1 G37R Wong et_amp_#xa0 al. 1995 and hSOD1 G93A Gurney et_amp_#xa0 al. 1994 and Howland et_amp_#xa0 al. 2002 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | and Howland et_amp_#xa0 al. 2002 as well as inactive (hSOD1 hSOD1 G85R Bruijn et_amp_#xa0 al. 1997 mSOD1 G86R Ripps et_amp_#xa0 al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 4.2 | well as inactive (hSOD1 hSOD1 G85R Bruijn et_amp_#xa0 al. 1997 mSOD1 G86R Ripps et_amp_#xa0 al. 1995 hSOD1 G127X Jonsson et_amp_#xa0 al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | Bruijn et_amp_#xa0 al. 1997 mSOD1 G86R Ripps et_amp_#xa0 al. 1995 hSOD1 G127X Jonsson et_amp_#xa0 al. 2004 hSOD1 Quad Wang et_amp_#xa0 al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | Ripps et_amp_#xa0 al. 1995 hSOD1 G127X Jonsson et_amp_#xa0 al. 2004 hSOD1 Quad Wang et_amp_#xa0 al. 2003 hSOD1 H46R Nagai et_amp_#xa0 al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | Jonsson et_amp_#xa0 al. 2004 hSOD1 Quad Wang et_amp_#xa0 al. 2003 hSOD1 H46R Nagai et_amp_#xa0 al. 2001 forms of the enzyme develop |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Furthermore SOD1 gene deletion in mice does not lead to motor neuron |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | In addition deletion of the endogenous mouse SOD1 in mice expressing dismutase inactive hSOD1 G85R does not affect |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | of the endogenous mouse SOD1 in mice expressing dismutase inactive hSOD1 G85R does not affect disease course ( Bruijn et_amp_#xa0 al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Mice expressing high levels of wild-type human SOD1 (hSOD1 hSOD1 WT transgene are healthy ( Gurney et_amp_#xa0 al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | Mice expressing high levels of wild-type human SOD1 (hSOD1 hSOD1 WT transgene are healthy ( Gurney et_amp_#xa0 al. 1994 and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | Indeed increased hSOD1 WT accompanied by chronic elevation of dismutase activity has either |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | SOD1 activity is dependent on a catalytic copper |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | is highly reactive and toxic it must be loaded onto SOD1 by a copper chaperone for SOD1 (CCS; CCS Corson et_amp_#xa0 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | must be loaded onto SOD1 by a copper chaperone for SOD1 (CCS; CCS Corson et_amp_#xa0 al. 1998 and Wong et_amp_#xa0 al. |
| 1613 | CCS | copper chaperone for superoxide dismutase | CCS | 1.7 | loaded onto SOD1 by a copper chaperone for SOD1 (CCS; CCS Corson et_amp_#xa0 al. 1998 and Wong et_amp_#xa0 al. 2000b and |
| 1613 | CCS | copper chaperone for superoxide dismutase | CCS | 1.7 | by a conserved disulfide bond whose formation is catalyzed by CCS ( Furukawa et_amp_#xa0 al. 2004 |
| 1613 | CCS | copper chaperone for superoxide dismutase | CCS | 1.7 | Since CCS is abundantly expressed in motor neurons ( Rothstein et_amp_#xa0 al. |
| 1613 | CCS | copper chaperone for superoxide dismutase | CCS | 1.7 | neurons ( Rothstein et_amp_#xa0 al. 1999 and motor neurons of CCS -deleted mice have an increased sensitivity to axotomy-induced death ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | 2002 it was postulated that inefficient incorporation of copper into SOD1 and/or and or a decreased shielding of copper (due due |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | a decreased shielding of copper (due due to changes in SOD1 structure as a result of mutation could provide an opportunity |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | using mice in which the incorporation of copper into mutant SOD1 was significantly reduced by disruption of the CCS gene |
| 1613 | CCS | copper chaperone for superoxide dismutase | CCS | 1.7 | into mutant SOD1 was significantly reduced by disruption of the CCS gene |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | in which all four copper-binding histidines have been eliminated (hSOD1 hSOD1 Quad resulting in dismutase inactive SOD1 still develop typical ALS-like |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | have been eliminated (hSOD1 hSOD1 Quad resulting in dismutase inactive SOD1 still develop typical ALS-like motor neuron disease ( Wang et_amp_#xa0 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | toxic property (or or properties acquired as a result of SOD1 mutation (1) 1 are independent of dismutase and CCS activities |
| 1613 | CCS | copper chaperone for superoxide dismutase | CCS | 1.7 | of SOD1 mutation (1) 1 are independent of dismutase and CCS activities and (2) 2 can be generated without catalysis by |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Misfolded SOD1 as a Common Feature of ALS-Causing Mutations |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | sporadic and familial ALS cases as well as in mutant SOD1 transgenic mice ( Bruijn et_amp_#xa0 al. 1997 Bruijn et_amp_#xa0 al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | used to define accumulations of detergent-insoluble forms of proteins including SOD1 that are detected by immunoblotting of filter-trappable material as well |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1- | 4.5 | detected by immunoblotting of filter-trappable material as well as small SOD1- or ubiquitin-positive fibrillar inclusions in spinal cord sections ( Deng |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Detergent-insoluble species are detectable only in affected tissues of mutant SOD1 mice and are most prominent at symptomatic stages ( Furukawa |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | A propensity to form aggregates following synthesis of mutant SOD1 in primary cells is selective to motor neurons as aggregates |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | The most misfolded unstable SOD1 mutants (with with the shortest in vivo half-lives are most |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | unexplained aspect of disease is that the very unstable mutant hSOD1 A4V ( Sato et_amp_#xa0 al. 2005 which provokes a very |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | in mice except in the context of high levels of hSOD1 WT ( Deng et_amp_#xa0 al. 2006 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | Similarly increased hSOD1 WT accelerated disease from a second unstable mutant hSOD1 L126Z |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | increased hSOD1 WT accelerated disease from a second unstable mutant hSOD1 L126Z |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | be mediated by_amp_#xa0 stabilization of the mutant via heterodimerization with_amp_#xa0 hSOD1 WT protein |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | Indeed in both cases increased levels_amp_#xa0 of hSOD1 WT generated detergent-insoluble forms of SOD1 that were not seen |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | cases increased levels_amp_#xa0 of hSOD1 WT generated detergent-insoluble forms of SOD1 that were not seen in spinal cord extracts of hSOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | SOD1 that were not seen in spinal cord extracts of hSOD1 A4V or hSOD1 L126Z mice alone |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | not seen in spinal cord extracts of hSOD1 A4V or hSOD1 L126Z mice alone |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Are SOD1 Aggregates Toxic |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Indeed the degradation of SOD1 itself and aggregates of SOD1 is proteasome mediated ( Basso |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Indeed the degradation of SOD1 itself and aggregates of SOD1 is proteasome mediated ( Basso et_amp_#xa0 al. 2006 Niwa et_amp_#xa0 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | In hSOD1 G93A mice which accumulate mutant protein to high levels proteasome |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | HSPs | 0.6 | examined the protein folding chaperone machinery the heat-shock proteins (HSPs), HSPs in the context of disease |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | been reported which persists throughout disease course and multiple recombinant SOD1 mutants inhibit chaperone function in vitro ( Bruening et_amp_#xa0 al. |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | HSPs | 0.6 | Paradoxically some HSPs such as _amp_#x3b1 B-crystallin and Hsp27 are elevated in the |
| 5246 | HSPB1 | heat shock 27kDa protein 1 | Hsp27 | 3.4 | Paradoxically some HSPs such as _amp_#x3b1 B-crystallin and Hsp27 are elevated in the spinal cords of hSOD1 G37R and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | B-crystallin and Hsp27 are elevated in the spinal cords of hSOD1 G37R and hSOD1 G93A mice but Hsp27 is predominantly present |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | are elevated in the spinal cords of hSOD1 G37R and hSOD1 G93A mice but Hsp27 is predominantly present in glial cells |
| 5246 | HSPB1 | heat shock 27kDa protein 1 | Hsp27 | 3.4 | spinal cords of hSOD1 G37R and hSOD1 G93A mice but Hsp27 is predominantly present in glial cells in late disease stages |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | Hsp70 | 0.6 | Hsp70 Hsp40 and Hsp90 are also elevated but only in the |
| 5270 | DNAJB1 | DnaJ (Hsp40) homolog, subfamily B, member 1 | Hsp40 | 1.0 | Hsp70 Hsp40 and Hsp90 are also elevated but only in the spinal |
| 5253 | HSP90AA1 | heat shock protein 90kDa alpha (cytosolic), class A member 1 | Hsp90 | 1.6 | Hsp70 Hsp40 and Hsp90 are also elevated but only in the spinal cords of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | are also elevated but only in the spinal cords of hSOD1 G85R mice ( Liu et_amp_#xa0 al. 2005 Vleminckx et_amp_#xa0 al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 4.5 | Mutant SOD1-mediated depletion of HSPs is a plausible possibility given that Hsp70 |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | HSPs | 0.6 | Mutant SOD1-mediated depletion of HSPs is a plausible possibility given that Hsp70 and Hsp25 preferentially |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | Hsp70 | 0.6 | SOD1-mediated depletion of HSPs is a plausible possibility given that Hsp70 and Hsp25 preferentially bind mutant SOD1 ( Okado-Matsumoto and Fridovich |
| 5246 | HSPB1 | heat shock 27kDa protein 1 | Hsp25 | 3.1 | of HSPs is a plausible possibility given that Hsp70 and Hsp25 preferentially bind mutant SOD1 ( Okado-Matsumoto and Fridovich 2002 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | plausible possibility given that Hsp70 and Hsp25 preferentially bind mutant SOD1 ( Okado-Matsumoto and Fridovich 2002 |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | HSPs | 0.6 | Expression of several different HSPs (Hsp70, Hsp70 Hsp40 Hsp27 in cultured cells and primary motor |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | Hsp70 | 0.6 | Expression of several different HSPs (Hsp70, Hsp70 Hsp40 Hsp27 in cultured cells and primary motor neurons decreases |
| 5270 | DNAJB1 | DnaJ (Hsp40) homolog, subfamily B, member 1 | Hsp40 | 1.0 | Expression of several different HSPs (Hsp70, Hsp70 Hsp40 Hsp27 in cultured cells and primary motor neurons decreases aggregate |
| 5246 | HSPB1 | heat shock 27kDa protein 1 | Hsp27 | 3.4 | Expression of several different HSPs (Hsp70, Hsp70 Hsp40 Hsp27 in cultured cells and primary motor neurons decreases aggregate content |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | Hsp70 | 0.6 | Unfortunately applying this strategy in vivo by increased expression of Hsp70 in four different mutant SOD1 mouse lines did not ameliorate |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | vivo by increased expression of Hsp70 in four different mutant SOD1 mouse lines did not ameliorate disease or pathology ( Liu |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | stress response extended life span in a small cohort of hSOD1 G93A mice after treatment with arimoclomol a drug which induces |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | HSP | 0.6 | arimoclomol a drug which induces the phosphorylation-mediated activation of the HSP inducing factor HSF-1 thereby leading to increased levels of Hsp70 |
| 5224 | HSF1 | heat shock transcription factor 1 | HSF-1 | 0.9 | which induces the phosphorylation-mediated activation of the HSP inducing factor HSF-1 thereby leading to increased levels of Hsp70 and Hsp90 in |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | Hsp70 | 0.6 | HSP inducing factor HSF-1 thereby leading to increased levels of Hsp70 and Hsp90 in spinal cords ( Kieran et_amp_#xa0 al. 2004 |
| 5253 | HSP90AA1 | heat shock protein 90kDa alpha (cytosolic), class A member 1 | Hsp90 | 1.6 | factor HSF-1 thereby leading to increased levels of Hsp70 and Hsp90 in spinal cords ( Kieran et_amp_#xa0 al. 2004 |
| 5246 | HSPB1 | heat shock 27kDa protein 1 | Hsp27 | 3.4 | Interestingly missense mutations in the gene encoding Hsp27 have been identified in a number of families with distal |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | that develop disease from accumulation of dismutase active mutants (hSOD1 hSOD1 G37R Wong et_amp_#xa0 al. 1995 and hSOD1 G93A mice Dal |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | active mutants (hSOD1 hSOD1 G37R Wong et_amp_#xa0 al. 1995 and hSOD1 G93A mice Dal Canto and Gurney 1994 Higgins et_amp_#xa0 al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | been described in mice with very high accumulated levels of hSOD1 WT protein ( Jaarsma et_amp_#xa0 al. 2000 and Jaarsma et_amp_#xa0 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | A proportion of the predominantly cytosolic SOD1 localizes to mitochondria in certain contexts |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | In both rodent models and patient samples mutant SOD1 is present in fractions enriched for mitochondria derived from affected |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Mitochondrial localization of SOD1 has been confirmed by electron microscopy in both isolated mitochondria |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | SOD1 mutants that cause disease at the lowest accumulated levels (hSOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | mutants that cause disease at the lowest accumulated levels (hSOD1 hSOD1 G85R and hSOD1 G127X all dismutase inactive have the highest |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | disease at the lowest accumulated levels (hSOD1 hSOD1 G85R and hSOD1 G127X all dismutase inactive have the highest relative proportions that |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | disagreement in defining the submitochondrial compartment(s) compartment s with which SOD1 is localized (or or potentially aggregated |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Mutant SOD1 has been reported in both the intermembrane space and the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | apparent contradictions remain to be resolved all reports agree that SOD1 mutant proteins of divergent biochemical characteristics localize to mitochondria consistent |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | there some intrinsic feature of spinal cord mitochondria which permits SOD1 association and/or and or increases mitochondrial vulnerability to mutant SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | SOD1 association and/or and or increases mitochondrial vulnerability to mutant SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Of relevance here the endogenous wild-type SOD1 protein is largely excluded from spinal cord mitochondria but all |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | is largely excluded from spinal cord mitochondria but all human SOD1 mutants examined to date are mitochondrially associated |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Liu et_amp_#xa0 al. 2004 despite a proportion of endogenous mouse SOD1 localized to the intermembrane space of those mitochondria ( Liu |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | How mutant SOD1 affects mitochondrial function is not yet clear but differences in |
| 13209 | ARHGEF5 | Rho guanine nucleotide exchange factor (GEF) 5 | TIM | 0.3 | translocators of the outer and inner membrane (TOM TOM and TIM respectively |
| 15860 | PRPF6 | PRP6 pre-mRNA processing factor 6 homolog (S. cerevisiae) | TOM | 0.1 | membrane-spanning multisubunit translocators of the outer and inner membrane (TOM TOM and TIM respectively |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Mutant SOD1 associated with or aggregated onto the mitochondrial surface could impede |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | example ATP synthesis has been reported as unchanged in aged hSOD1 G85R mice ( Damiano et_amp_#xa0 al. 2006 or depleted in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | ( Damiano et_amp_#xa0 al. 2006 or depleted in late symptomatic hSOD1 G93A mice ( Mattiazzi et_amp_#xa0 al. 2002 or ATP levels |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | Creatine which extended survival in hSOD1 G93A mice by alleviating presumed energy deficits ( Browne et_amp_#xa0 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Early impairment in mitochondrial calcium-buffering capacity in mutant SOD1 spinal cord prior to symptoms and only in disease-relevant tissues |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | symptoms and only in disease-relevant tissues in two different mutant SOD1 models ( Damiano et_amp_#xa0 al. 2006 is perhaps the most |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 1.0 | Pasinelli et_amp_#xa0 al. 2000 and lowered levels of the antiapoptotic Bcl-2 have been reported in spinal cord motor neurons of ALS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | et_amp_#xa0 al. 1999 and Mu et_amp_#xa0 al. 1996 and mutant SOD1 mice ( Gonzalez de Aguilar et_amp_#xa0 al. 2000 and Vukosavic |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | EAAT2 | 2.8 | caspase-3 activation in glial cells proteolytically inactivates the glutamate transporter EAAT2 ( Boston-Howes et_amp_#xa0 al. 2006 |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | EAAT2 | 2.8 | Since EAAT2 is selectively lost during the disease process and is considered |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | An alternate mechanism in which SOD1 is proposed to interact with Bcl-2 and possibly interferes with |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 1.0 | alternate mechanism in which SOD1 is proposed to interact with Bcl-2 and possibly interferes with Bcl-2 antiapoptotic activity ( Pasinelli et_amp_#xa0 |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 1.0 | is proposed to interact with Bcl-2 and possibly interferes with Bcl-2 antiapoptotic activity ( Pasinelli et_amp_#xa0 al. 2004 is attractive but |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 1.0 | However both constitutively increased expression of Bcl-2 ( Kostic et_amp_#xa0 al. 1997 and virally driven overexpression of |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 1.0 | ( Kostic et_amp_#xa0 al. 1997 and virally driven overexpression of Bcl-2 in motor neurons ( Azzouz et_amp_#xa0 al. 2000 protect motor |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 1.0 | Bcl-2 is unable to similarly rescue motor neuron death in other |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | NF-L | 2.4 | wobbler and transgenic mice expressing a point mutation in the NF-L gene ( Coulpier et_amp_#xa0 al. 1996 and Houseweart and Cleveland |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 4.5 | spectrum caspase inhibitor ( Li et_amp_#xa0 al. 2000 slowed mutant SOD1-mediated neuronal death disease onset was also delayed in the absence |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | different subsets of muscle fibers have different susceptibilities to mutant SOD1 toxicity |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Specifically in two different mutant SOD1 models the fast-fatiguable motor neurons were shown to be affected |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | followed next with the slow type partially resistant to mutant SOD1 and actually attempting to reinnervate previously denervated regions ( Frey |
| 12499 | UBE4A | ubiquitination factor E4A (UFD2 homolog, yeast) | UFD2 | 2.1 | containing the first 70 residues of the ubiquitination factor UFD2/E4 UFD2 E4 joined to mononucleotide adenylyltransferase (Nmnat), Nmnat an enzyme that |
| 17877 | NMNAT1 | nicotinamide nucleotide adenylyltransferase 1 | Nmnat | 1.9 | ubiquitination factor UFD2/E4 UFD2 E4 joined to mononucleotide adenylyltransferase (Nmnat), Nmnat an enzyme that facilitates nicotinamide adenine dinucleotide (NAD) NAD synthesis |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | s failed to provide a benefit in three different mutant SOD1 models ( Fischer et_amp_#xa0 al. 2005 and Vande Velde et_amp_#xa0 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | et_amp_#xa0 al. 1984b and Kawamura et_amp_#xa0 al. 1981 and mutant SOD1 mice ( Bruijn et_amp_#xa0 al. 1998 Kong and Xu 1998 |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | NF-L | 2.4 | Neurofilaments are obligate heteropolymers of NF light (NF-L), NF-L NF medium (NF-M), NF-M and NF heavy (NF-H) NF-H subunits |
| 7734 | NEFM | neurofilament, medium polypeptide 150kDa | NF-M | 1.9 | obligate heteropolymers of NF light (NF-L), NF-L NF medium (NF-M), NF-M and NF heavy (NF-H) NF-H subunits and interestingly transgenic mice |
| 7737 | NEFH | neurofilament, heavy polypeptide 200kDa | NF-H | 0.9 | (NF-L), NF-L NF medium (NF-M), NF-M and NF heavy (NF-H) NF-H subunits and interestingly transgenic mice expressing a point mutation in |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | NF-L | 2.4 | subunits and interestingly transgenic mice expressing a point mutation in NF-L develop motor neuron disease ( Lee et_amp_#xa0 al. 1994 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Neurofilament accumulations are seen early in mutant SOD1 mice ( Kong and Xu 1998 |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | NF-L | 2.4 | Removal of all axonal neurofilaments by deletion of NF-L substantially prolonged survival of hSOD1 G85R and hSOD1 G37R mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | axonal neurofilaments by deletion of NF-L substantially prolonged survival of hSOD1 G85R and hSOD1 G37R mice ( Nguyen et_amp_#xa0 al. 2001 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | deletion of NF-L substantially prolonged survival of hSOD1 G85R and hSOD1 G37R mice ( Nguyen et_amp_#xa0 al. 2001 and Williamson et_amp_#xa0 |
| 7737 | NEFH | neurofilament, heavy polypeptide 200kDa | NF-H | 0.9 | did removal of most axonal neurofilaments by excessive levels of NF-H ( Couillard-Despres et_amp_#xa0 al. 1998 Kong and Xu 2000 and |
| 7734 | NEFM | neurofilament, medium polypeptide 150kDa | NF-M | 1.9 | gene replacement to remove the phosphorylated _amp_#x201c tail_amp_#x201d domains of NF-M and NF-H that normally provide intra-axonal crosslinking of adjacent filaments |
| 7737 | NEFH | neurofilament, heavy polypeptide 200kDa | NF-H | 0.9 | to remove the phosphorylated _amp_#x201c tail_amp_#x201d domains of NF-M and NF-H that normally provide intra-axonal crosslinking of adjacent filaments |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Absence of those tail domains sharply slows SOD1 mutant-induced disease ( Lobsiger et_amp_#xa0 al. 2005 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | deficit of slow axonal transport has been described in mutant SOD1 mice ( Ackerley et_amp_#xa0 al. 2003 Williamson and Cleveland 1999 |
| 8982 | PIK3R4 | phosphoinositide-3-kinase, regulatory subunit 4 | p150 | 1.3 | disease arose from the discovery of a mutation in the p150 Glued subunit of dynactin in a family affected with a |
| 8982 | PIK3R4 | phosphoinositide-3-kinase, regulatory subunit 4 | p150 | 1.3 | of lower motor neuron disease ( Puls et_amp_#xa0 al. 2003 p150 Glued is responsible for providing processivity by bridging between microtubules |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | 2005 or Cra1 ( Teuchert et_amp_#xa0 al. 2006 mutation to hSOD1 G93A mice significantly improves survival |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | This unexpected amelioration of SOD1 mutant toxicity by a mutation expected to alter retrograde axonal |
| 6323 | KIF5A | kinesin family member 5A | KIF5A | 0.6 | CMT type 2A ( Zhao et_amp_#xa0 al. 2001 loss of KIF5A in hereditary spastic paraplegia ( Reid et_amp_#xa0 al. 2002 and |
| 19349 | KIF21A | kinesin family member 21A | KIF21A | 0.6 | spastic paraplegia ( Reid et_amp_#xa0 al. 2002 and loss of KIF21A in a rare disorder affecting the oculomotor nerve ( Yamada |
| 12649 | VAPB | VAMP (vesicle-associated membrane protein)-associated protein B and C | ALS8 | 3.6 | in genes involved in transport of membranous vesicles include the ALS8 gene VAPB ( Nishimura et_amp_#xa0 al. 2004b Rab7 in CMT |
| 12649 | VAPB | VAMP (vesicle-associated membrane protein)-associated protein B and C | VAPB | 4.2 | involved in transport of membranous vesicles include the ALS8 gene VAPB ( Nishimura et_amp_#xa0 al. 2004b Rab7 in CMT type 2B |
| 9788 | RAB7A | RAB7A, member RAS oncogene family | Rab7 | 1.0 | include the ALS8 gene VAPB ( Nishimura et_amp_#xa0 al. 2004b Rab7 in CMT type 2B ( Verhoeven et_amp_#xa0 al. 2003 and |
| 18652 | VPS54 | vacuolar protein sorting 54 homolog (S. cerevisiae) | Vps54 | 0.6 | in CMT type 2B ( Verhoeven et_amp_#xa0 al. 2003 and Vps54 (vacuolar-vesicular vacuolar-vesicular protein sorting 54 which is responsible for cervical |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | caused by mutations in genes that are ubiquitously expressed ( SOD1 and VAPB or expressed in multiple cells types ( VEGF |
| 12649 | VAPB | VAMP (vesicle-associated membrane protein)-associated protein B and C | VAPB | 4.2 | mutations in genes that are ubiquitously expressed ( SOD1 and VAPB or expressed in multiple cells types ( VEGF and ANG |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | SOD1 and VAPB or expressed in multiple cells types ( VEGF and ANG |
| 483 | ANG | angiogenin, ribonuclease, RNase A family, 5 | ANG | 0.6 | VAPB or expressed in multiple cells types ( VEGF and ANG |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | type was required for disease came from expression of mutant SOD1 only within motor neurons ( Lino et_amp_#xa0 al. 2002 and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | neuron degeneration or death (albeit albeit the expression of mutant SOD1 selectively within motor neurons might have been at levels too |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | construction and analysis of chimeric mice that were mixtures of hSOD1 mutant-expressing cells and normal cells ( Clement et_amp_#xa0 al. 2003 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | These efforts conclusively demonstrated that expression of mutant SOD1 within individual motor neurons even at levels that cause early |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | analysis of mice carrying a deletable (_amp_#x201c;floxed_amp_#x201d;) _amp_#x201c floxed_amp_#x201d mutant SOD1 gene that can be excised by the action of the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Excision of the floxed mutant SOD1 gene exclusively within motor neurons (by by action of Cre |
| 7734 | NEFM | neurofilament, medium polypeptide 150kDa | NF-M | 1.9 | and volume after elimination of the tail domains of the NF-M and NF-H subunits Lobsiger et_amp_#xa0 al. 2005 provide extended survival |
| 7737 | NEFH | neurofilament, heavy polypeptide 200kDa | NF-H | 0.9 | after elimination of the tail domains of the NF-M and NF-H subunits Lobsiger et_amp_#xa0 al. 2005 provide extended survival of SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | NF-H subunits Lobsiger et_amp_#xa0 al. 2005 provide extended survival of SOD1 mutant mice but only by slowing disease onset |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | In contrast diminishing mutant SOD1 levels within microglia and peripheral macrophages (using using a Cre |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | CD11b | 1.0 | and peripheral macrophages (using using a Cre transgene with a CD11b promoter that is expressed only within the microglia and peripheral |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | was replaced by transplantation of normal bone marrow cells into SOD1 mutant mice that were themselves unable to synthesize their own |
| 11241 | SPI1 | spleen focus forming virus (SFFV) proviral integration oncogene spi1 | PU.1 | 1.0 | own myeloid cells due to deletion of the transcription factor PU.1 ( Beers et_amp_#xa0 al. 2006 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | Transplantation at birth_amp_#xa0 with hSOD1 G93A mutant-expressing myeloid cells (which which populate both the CNS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | and the periphery produced onset and survival typical of the hSOD1 G93A mutant line |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Thus both approaches demonstrated that mutant SOD1 within macrophages/microglial macrophages microglial cells accelerates disease progression while mutant |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-expressing | 4.2 | Importantly introducing mutant SOD1-expressing microglial cells into control animals did not give rise to |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-expressing | 4.2 | not give rise to motor neuron disease demonstrating that mutant SOD1-expressing macrophages/microglial macrophages microglial cells themselves are not sufficient to cause |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | macrophages/microglial macrophages microglial cells in the spinal cord of mutant SOD1 mice have been shown to enter from the periphery during |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | al. 2004 and in the spinal cord of different mutant SOD1 mouse models ( Hall et_amp_#xa0 al. 1998 Henkel et_amp_#xa0 al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | have been reported in spinal cords of ALS patients and hSOD1 G93A mice during the disease course ( Henkel et_amp_#xa0 al. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | Cyclooxygenase-2 (COX-2), COX-2 produced in abundance by microglia and other inflammatory cells (but |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | a key role in stimulating production of proinflammatory cytokines and COX-2 expression is induced in spinal cords of ALS patients ( |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | In mice use of a COX-2 inhibitor (celecoxib) celecoxib prolonged survival by slowing disease onset ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Such treatment exacerbated SOD1 mutant-mediated disease in mice ( Nguyen et_amp_#xa0 al. 2004 |
| 10647 | CX3CL1 | chemokine (C-X3-C motif) ligand 1 | fractalkine | 1.0 | Similarly inducing microglial activation by deleting the fractalkine receptor a cytokine receptor expressed by microglia mildly accelerated neuronal |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | receptor expressed by microglia mildly accelerated neuronal loss in mutant SOD1 mice ( Cardona et_amp_#xa0 al. 2006 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | factors have been described in the spinal cords of mutant SOD1 mice even before motor neuron loss ( Elliott 2001 Hensley |
| 6953 | CD46 | CD46 molecule, complement regulatory protein | MCP-1_amp_#x3b1 | 0.3 | related factors including complement proteins and monocyte chemoattractant protein-1_amp_#x3b1 (MCP-1_amp_#x3b1;; MCP-1_amp_#x3b1 Goldknopf et_amp_#xa0 al. 2006 and Simpson et_amp_#xa0 al. 2004 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | One particularly interesting cytokine upregulated in mutant SOD1 mouse spinal cords which could play a role in motor |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | been shown to be produced in higher levels by adult hSOD1 G93A microglial cells when stimulated with LPS compared to nontransgenic |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | TNF_amp_#x3b1 antagonist yielded a mild increase in survival in mutant SOD1 mice ( West et_amp_#xa0 al. 2004 |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas-ligand | 0.3 | Microglial cells could therefore be an important player in a Fas-ligand (FasL)-induced FasL -induced apoptosis pathway within motor neurons that is |
| 11936 | FASLG | Fas ligand (TNF superfamily, member 6) | FasL | 1.6 | could therefore be an important player in a Fas-ligand (FasL)-induced FasL -induced apoptosis pathway within motor neurons that is driven by |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | In addition mutant SOD1 which has now been reported to be released by motor |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | a partial explanation for the selectivity of motor neurons to SOD1 mutant toxicity has arisen from identification of a motor-neuron-specific cell-death |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | surprisingly embryonic motor neurons extracted from spinal cords of mutant SOD1 mice are more susceptible to toxic insults ( Kruman et_amp_#xa0 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | neurons from normal mice or mice expressing high levels of hSOD1 WT protein |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas | 0.3 | been proposed as a motor-neuron-specific cell-death pathway downstream of the Fas death receptor |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas | 0.3 | Increased susceptibility to death triggered by the Fas receptor requires nitric oxide the Fas death domain-associated protein Daxx |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas | 0.3 | death triggered by the Fas receptor requires nitric oxide the Fas death domain-associated protein Daxx and p38 kinase activation which subsequently |
| 2681 | DAXX | death-associated protein 6 | Daxx | 0.8 | Fas receptor requires nitric oxide the Fas death domain-associated protein Daxx and p38 kinase activation which subsequently drives nitric oxide production |
| 1189 | AHSA1 | AHA1, activator of heat shock 90kDa protein ATPase homolog 1 (yeast) | p38 | 0.6 | requires nitric oxide the Fas death domain-associated protein Daxx and p38 kinase activation which subsequently drives nitric oxide production thus generating |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Cultured motor neurons from transgenic mutant SOD1 mice have an increased susceptibility to activation of this pathway |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | acceleration of disease by mutant microglia it is plausible that SOD1 mutant-induced release of nitric oxide by microglia drives this death |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | EAAT2 | 2.8 | synaptic glutamate through the action of the glial glutamate transporter EAAT2 (also also referred to as GLT-1 in rodents |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | GLT-1 | 2.8 | the glial glutamate transporter EAAT2 (also also referred to as GLT-1 in rodents |
| 4572 | GRIA2 | glutamate receptor, ionotropic, AMPA 2 | GluR2 | 1.3 | since their glutamate receptors have a lower proportion of the GluR2 subunit ( Van Damme et_amp_#xa0 al. 2002 relative to many |
| 4572 | GRIA2 | glutamate receptor, ionotropic, AMPA 2 | GluR2 | 1.3 | Regulation of the Ca 2 permeability properties of GluR2 is due to posttranscriptional RNA editing with only AMPA receptors |
| 4572 | GRIA2 | glutamate receptor, ionotropic, AMPA 2 | GluR2 | 1.3 | to posttranscriptional RNA editing with only AMPA receptors containing edited GluR2 resistant to Ca 2 entry |
| 4572 | GRIA2 | glutamate receptor, ionotropic, AMPA 2 | GluR2 | 1.3 | Already with low GluR2 levels the efficiency of mRNA editing is reduced in the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | Altered efficiency of editing was not found in hSOD1 G93A or hSOD1 H46R rats ( Kawahara et_amp_#xa0 al. 2006 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | efficiency of editing was not found in hSOD1 G93A or hSOD1 H46R rats ( Kawahara et_amp_#xa0 al. 2006 thereby demonstrating that |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.8 | their intermediate filaments (assembled assembled from glial fibrillary acidic protein GFAP and an increase in the number and size of processes |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | activation is seen in spinal cords of ALS patients and SOD1 mutant mice ( Hall et_amp_#xa0 al. 1998 Levine et_amp_#xa0 al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | Indeed for mice expressing the dismutase inactive mutant hSOD1 G85R a very prominent early pathology that increases markedly during |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-containing | 4.2 | that increases markedly during disease course is the presence of SOD1-containing inclusions within activated astrocytes ( Bruijn et_amp_#xa0 al. 1997 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | one of the few firm mechanistic links between sporadic and SOD1 mutant-caused ALS |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | EAAT2 | 2.8 | ALS patients ( Rothstein et_amp_#xa0 al. 1992 and levels of EAAT2 are reduced in the motor cortex and spinal cord of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | 1995 and Sasaki et_amp_#xa0 al. 2000 spinal cords of mutant SOD1 mice ( Bruijn et_amp_#xa0 al. 1997 and rats ( Howland |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | This is functionally of consequence for familial ALS in that hSOD1 G93A mice heterozygous for EAAT2 develop earlier-onset disease ( Pardo |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | EAAT2 | 2.8 | for familial ALS in that hSOD1 G93A mice heterozygous for EAAT2 develop earlier-onset disease ( Pardo et_amp_#xa0 al. 2006 while drugs |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | EAAT2 | 2.8 | disease ( Pardo et_amp_#xa0 al. 2006 while drugs that increase EAAT2 activity extend survival ( Ganel et_amp_#xa0 al. 2006 and Rothstein |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | EAAT2 | 2.8 | Indeed screening of FDA-approved drugs for those that_amp_#xa0 could elevate EAAT2 activity has identified_amp_#xa0 a CNS-penetrating _amp_#x3b2 -lactam antibiotic ceftriaxone as_amp_#xa0 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | ceftriaxone as_amp_#xa0 a transcriptional inducer that modestly extends survival in hSOD1 G93A mice ( Rothstein et_amp_#xa0 al. 2005 |
| 7808 | NGF | nerve growth factor (beta polypeptide) | NGF | 0.6 | astrocytes induce embryonic motor neuron degeneration via their production of NGF which in the presence of low concentrations of nitric oxide |
| 11917 | TNFRSF1B | tumor necrosis factor receptor superfamily, member 1B | p75 | 1.2 | nitric oxide can induce apoptosis of motor neurons through the p75 NTR receptor |
| 11917 | TNFRSF1B | tumor necrosis factor receptor superfamily, member 1B | NTR | 0.2 | oxide can induce apoptosis of motor neurons through the p75 NTR receptor |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | to resting astrocytes activated astrocytes in the spinal cord of hSOD1 G93A mice have increased NGF synthesis ( Pehar et_amp_#xa0 al. |
| 7808 | NGF | nerve growth factor (beta polypeptide) | NGF | 0.6 | in the spinal cord of hSOD1 G93A mice have increased NGF synthesis ( Pehar et_amp_#xa0 al. 2004 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 4.5 | Among the earliest events in the human ALS- and SOD1-mediated disease is withdrawal of the motor axons from the neuromuscular |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Mutant SOD1 is also expressed by muscle but whether its presence there |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | beneficial in ALS has been attempted by repetitive injection into hSOD1 G93A mice of an antibody to myostatin a secreted protein |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | hypertrophy induced by agents such as insulin-like growth factor-1 (IGF-1) IGF-1 or growth hormone ( Dobrowolny et_amp_#xa0 al. 2005 Kaspar et_amp_#xa0 |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | For the IGF-1 studies not only was there muscle hypertrophy but also concomitant |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | Although in one instance IGF-1 synthesis was mediated by a transgene expressed only by the |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | al. 2005 it has not been established if the secreted IGF-1 acts on the muscle the motor neuron or both |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | al. 2003 and Veldink et_amp_#xa0 al. 2003 with_amp_#xa0 exercise and IGF-1 exhibiting a synergistic effect resulting in an increase in median |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | During this phase mutant SOD1 primarily acts directly within motor neurons with aggregation of misfolded |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | primarily acts directly within motor neurons with aggregation of misfolded SOD1 damaging cellular machinery especially mitochondria so as to inhibit one |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | SOD1 mutant action within the motor neuron is amplified by action |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Misfolded SOD1 mutant within astrocytes as well as their activation in response |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | EAAT2 | 2.8 | activation in response to neuronal damage induces loss of the EAAT2 glutamate transporter reducing rapid recovery of synaptic glutamate and driving |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | SOD1 mutant action directly within microglial and astrocytic cells may provoke |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | of toxic factors (e.g., e.g. nitric oxide TNF_amp_#x3b1 or mutant SOD1 secreted or released by cell leakage or lysis |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Mutant SOD1 can itself activate microglia |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | EAAT2 | 2.8 | Loss of EAAT2 glutamate transporters from astrocytes drives repetitive firing of glutamate receptors |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Thus selective sensitivity of motor neurons to ubiquitously expressed SOD1 mutants derives from the combination of risk factors shared by |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | to nearly uniform disappointment providing little or no benefit for IGF-1 ( Borasio et_amp_#xa0 al. 1998 and Lai et_amp_#xa0 al. 1997 |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 0.3 | 1998 and Lai et_amp_#xa0 al. 1997 and no benefit for BDNF ( BDNF Study Group 1999 or CNTF ( ALS CNTF |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 0.3 | Lai et_amp_#xa0 al. 1997 and no benefit for BDNF ( BDNF Study Group 1999 or CNTF ( ALS CNTF Treatment Study |
| 2169 | CNTF | ciliary neurotrophic factor | CNTF | 0.3 | no benefit for BDNF ( BDNF Study Group 1999 or CNTF ( ALS CNTF Treatment Study Group 1996 |
| 2169 | CNTF | ciliary neurotrophic factor | CNTF | 0.3 | BDNF ( BDNF Study Group 1999 or CNTF ( ALS CNTF Treatment Study Group 1996 |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 0.3 | Continuous intrathecal administration of BDNF was found to be without benefit but ICV infusion of |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | was found to be without benefit but ICV infusion of IGF-1 extended survival in mice ( Nagano et_amp_#xa0 al. 2005a and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | Use of this strategy slowed disease progression in hSOD1 G93A mice even when initiated after disease onset ( Kaspar |
| 4232 | GDNF | glial cell derived neurotrophic factor | GDNF | 0.9 | The same AAV producing GDNF used in the same manner provided only a very modest |
| 4232 | GDNF | glial cell derived neurotrophic factor | GDNF | 0.9 | ( Kaspar et_amp_#xa0 al. 2003 consistent with prior efforts using GDNF encoded by adenovirus ( Acsadi et_amp_#xa0 al. 2002 or AAV |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | With the potential that variants in the VEGF gene contribute to some examples of ALS ( Table 1 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | ALS ( Table 1 delivery of an integrating lentivirus encoding VEGF (and and pseudocoated so as to be retrogradely transported extended |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | pseudocoated so as to be retrogradely transported extended survival of hSOD1 G93A mice ( Azzouz et_amp_#xa0 al. 2004 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | So too did continuous ICV infusion of recombinant VEGF protein into the CSF ( Figure_amp_#xa0 4 B disease onset |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | This ICV delivery of VEGF was especially effective in slowing forelimb paralysis suggestive of a |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | in slowing forelimb paralysis suggestive of a higher concentration of VEGF closer to the site of infusion |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | A modest benefit was seen even when VEGF treatment was initiated after symptomatic onset |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Unresolved is which cells are targeted by this VEGF |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Weekly intraperitoneal injection of VEGF also has been reported to slow disease in hSOD1 G93A |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | of VEGF also has been reported to slow disease in hSOD1 G93A mice ( Zheng et_amp_#xa0 al. 2004 raising the possibility |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | that the instances of ALS caused by dominant mutation in SOD1 derive from a toxic property of the mutant protein and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | efforts using siRNA to catalyze degradation of the mRNA encoding SOD1 have proven successful in hSOD1 G93A mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | degradation of the mRNA encoding SOD1 have proven successful in hSOD1 G93A mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | After retrograde transport to motor neuron cell bodies reducing SOD1 mutant synthesis in motor neurons had a remarkable effect in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | H This approach has been successfully used for lowering mutant SOD1 levels by 50% throughout the brain and at all levels |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | brain and at all levels of the spinal cord of hSOD1 G93A rats |
| 4232 | GDNF | glial cell derived neurotrophic factor | GDNF | 0.9 | grafting of neural stem cells expressing glial-derived neurotrophic factor (GDNF) GDNF into the nerve |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | Other strategies with hSOD1 G93A mice have used (1) 1 human neural stem cells |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | In hSOD1 G93A mice an increase in neural progenitor cell proliferation migration |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | was initiated on the predominantly symptomatic side of asymmetrically paralyzed hSOD1 G93A rats ( de Hemptinne et_amp_#xa0 al. 2006 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 4.2 | cell neuroprogenitor niches of the forebrain has revealed alterations in hSOD1 G93A mice ( Liu and Martin 2006 |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | precursors including those engineered to produce trophic factors such as IGF-1 are now sensible approaches |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Figure_amp_#xa0 1._amp_#xa0 Proposed Toxicities of ALS-Causing SOD1 Protein Aggregates |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-Mediated | 4.5 | Figure_amp_#xa0 2._amp_#xa0 Mutant SOD1-Mediated Damage to Mitochondria |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 7.8 | Motor Neuron Degeneration and Glial Activation during the Course of SOD1 Mutant-Initiated ALS Disease |
| 483 | ANG | angiogenin, ribonuclease, RNase A family, 5 | angiogenin | 1.0 | mutations in genes encoding angiogenin ang and vegf and sequence variants in neurofilament genes have also been reported for more detailed consideration of the genetics see gros louis et_amp_#xa0;al [2006] . |
| 483 | ANG | angiogenin, ribonuclease, RNase A family, 5 | angiogenin | 1.0 | although all have in common disease that affects motor neurons the nomenclature is misleading since only als1 als3 als6 als7 mutations in angiogenin and vegf and a small proportion of incidences of als8 represent the classic late onset neurodegenerative disease with selective killing of upper and lower motor neurons leading to progressive paralys |
| 12680 | VEGFA | vascular endothelial growth factor A | vascular endothelial growth factor | 1.0 | vascular endothelial growth factor vegf |
| 12680 | VEGFA | vascular endothelial growth factor A | vascular endothelial growth factor | 1.0 | vascular endothelial growth factor vegf an established regulator of developmental hypoxia induced and tumor induced angiogenesis gained interest as a contributor to als when deletion of the hypoxia response element hre in the murine v |
| 727 | ARTN | artemin | neurotrophic factor | 1.0 | vegf is widely expressed throughout the central nervous system cns and can function as a neurotrophic factor for multiple neuronal cell types including motor neurons oosthuyse et_amp_#xa0;al. 2001 and van den bosch et_amp_#xa0;al. 2004 . |
| 483 | ANG | angiogenin, ribonuclease, RNase A family, 5 | angiogenin | 1.0 | angiogenin ang |
| 483 | ANG | angiogenin, ribonuclease, RNase A family, 5 | angiogenin | 1.0 | the manner in which the identified mutations affect angiogenin function and provoke motor neuron disease is still unknown. |
| 483 | ANG | angiogenin, ribonuclease, RNase A family, 5 | angiogenin | 1.0 | angiogenin which is expressed within the cns including the motor neurons has a known intranuclear rnase activity that can facilitate rrna synthesis at least in endothelial cells. |
| 483 | ANG | angiogenin, ribonuclease, RNase A family, 5 | angiogenin | 1.0 | ingly the majority of the mutations found in als patients are located within the catalytic core and one of them is in the nuclear localization signal both predicting a loss of function of the mutated angiogenin although this remains to be confirmed. |
| 483 | ANG | angiogenin, ribonuclease, RNase A family, 5 | angiogenin | 1.0 | whether angiogenin is endowed with neurotrophic properties like vegf in addition to its angiogenic activity is not yet established. |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | nf l | 1.0 | in addition mice with increased levels of wild type nf h or nf l subunits develop age dependent motor neuron pathology cote et_amp_#xa0;al. 1993 and xu et_amp_#xa0;al. 1993 while expression of a point mutation in nf l at levels corresponding to that expected for d |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | nf l | 1.0 | subunits develop age dependent motor neuron pathology cote et_amp_#xa0;al. 1993 and xu et_amp_#xa0;al. 1993 while expression of a point mutation in nf l at levels corresponding to that expected for dominantly inherited disease produces fatal progressive paralysis lee et_amp_#xa0;al. 1994 . |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | nf l | 1.0 | ations in the three neurofilament genes in patient dnas failed to yield conclusive linkage to either sporadic or familial als patients garcia et_amp_#xa0;al. 2006 although dominant point mutations in nf l have been linked to a milder motor neuron disease charcot marie tooth cmt disease de jonghe et_amp_#xa0;al. 2001 and jordanova et_amp_#xa0;al. 2003 . |
| 9461 | PRPH | peripherin | peripherin | 1.0 | a proposal for the involvement of a peripherin variant in which an intronic sequence is retained in the final mrna that is_amp_#xa0;produced during the disease course may also contribute to human disease robertson et_amp_#xa0;al. 2003 albeit dele |
| 9461 | PRPH | peripherin | peripherin | 1.0 | which an intronic sequence is retained in the final mrna that is_amp_#xa0;produced during the disease course may also contribute to human disease robertson et_amp_#xa0;al. 2003 albeit deletion of the peripherin gene has no affect on disease course in mice having an als causing sod1 mutation lariviere et_amp_#xa0;al. 2003 . |
| 9461 | PRPH | peripherin | peripherin | 1.0 | in some instances it refers to abnormal accumulations of intermediate filaments including neurofilaments and peripherin as detected by immunostaining of spinal cord tissue hirano et_amp_#xa0;al. 1984b mendonca et_amp_#xa0;al. 2005 mizusawa et_amp_#xa0;al. 1989 rouleau et_amp_#xa0;al. 1996 sobue et_amp_#xa0;al. 1990 an |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | it has also been used to define accumulations of detergent insoluble forms of proteins including sod1 that are detected by immunoblotting of filter trappable material as well as small sod1 or ubiquitin positive fibrillar inclusions in spinal cord sections deng et_amp_#xa0;al. 2006 furukawa et_amp_#xa0;al. 2006 johnston et_amp_#xa0;al. 2000 jonsson et_amp_#xa0;al. 2004 jonsson et_amp_#xa0;al. 2006 w |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | aggregates found in als patients as well as mouse models contain ubiquitin ince et_amp_#xa0;al. 1998 wang et_amp_#xa0;al. 2003 and watanabe et_amp_#xa0;al. 2001 a protein adduct which typically targets proteins for disposal via the proteasome. |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | hsp70 | 1.0 | hsp70 hsp40 and hsp90 are also elevated but only in the spinal cords of hsod1 g85r mice liu et_amp_#xa0;al. 2005 vleminckx et_amp_#xa0;al. 2002 and wang et_amp_#xa0;al. 2003 . |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | hsp70 | 1.0 | mutant sod1 mediated depletion of hsps is a plausible possibility given that hsp70 and hsp25 preferentially bind mutant sod1 okado matsumoto and fridovich 2002 . |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | hsp70 | 1.0 | expression of several different hsps hsp70 hsp40 hsp27 in cultured cells and primary motor neurons decreases aggregate content and apoptosis and improves axonal outgrowth bruening et_amp_#xa0;al. 1999 patel et_amp_#xa0;al. 2005 and takeuchi e |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | hsp70 | 1.0 | unfortunately applying this strategy in vivo by increased expression of hsp70 in four different mutant sod1 mouse lines did not ameliorate disease or pathology liu et_amp_#xa0;al. 2005 . |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | hsp70 | 1.0 | a small cohort of hsod1 g93a mice after treatment with arimoclomol a drug which induces the phosphorylation mediated activation of the hsp inducing factor hsf 1 thereby leading to increased levels of hsp70 and hsp90 in spinal cords kieran et_amp_#xa0;al. 2004 . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | mitochondria are the gatekeepers of apoptosis with opening of the permeability transition pore and release of cytochrome c central to the cascade of caspase activation. |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | activation of the executioner caspase 3 is found in mouse models contemporaneous with neuronal death li et_amp_#xa0;al. 2000 and pasinelli et_amp_#xa0;al. 2000 and lowered levels of the antiapoptotic bcl 2 have been reported in spinal cord motor neurons of als patients ekegren et_amp_#xa0;al. 1999 and mu et_amp_#xa0;al. 1996 and mutant sod1 mice gonzalez de aguilar et_amp_#xa0;al. 2000 and vukosavic et |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | a final apoptotic mechanism is probably a central aspect of neuronal death as activation of the executioner caspase 3 is found in mouse models contemporaneous with neuronal death li et_amp_#xa0;al. 2000 and pasinelli et_amp_#xa0;al. 2000 and lowered levels of the antiapoptotic bcl 2 have been reported in spinal cord |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | intriguingly it has recently been demonstrated that caspase 3 activation in glial cells proteolytically inactivates the glutamate transporter eaat2 boston howes et_amp_#xa0;al. 2006 . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | an alternate mechanism in which sod1 is proposed to interact with bcl 2 and possibly interferes with bcl 2 antiapoptotic activity pasinelli et_amp_#xa0;al. 2004 is attractive but has recently been disputed gould et_amp_#xa0;al. 2006 . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | however both constitutively increased expression of bcl 2 kostic et_amp_#xa0;al. 1997 and virally driven overexpression of bcl 2 in motor neurons azzouz et_amp_#xa0;al. 2000 protect motor neurons delaying disease onset but not progression. |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | nf l | 1.0 | bcl 2 is unable to similarly rescue motor neuron death in other models such as wobbler and transgenic mice expressing a point mutation in the nf l gene coulpier et_amp_#xa0;al. 1996 and houseweart and cleveland 1999 . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | bcl 2 is unable to similarly rescue motor neuron death in other models such as wobbler and transgenic mice expressing a point mutation in the nf l gene coulpier et_amp_#xa0;al. 1996 and houseweart and clev |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | nf l | 1.0 | neurofilaments are obligate heteropolymers of nf light nf l nf medium nf m and nf heavy nf h subunits and interestingly transgenic mice expressing a point mutation in nf l develop motor neuron disease lee et_amp_#xa0;al. 1994 . |
| 7734 | NEFM | neurofilament, medium polypeptide 150kDa | nf m | 1.0 | neurofilaments are obligate heteropolymers of nf light nf l nf medium nf m and nf heavy nf h subunits and interestingly transgenic mice expressing a point mutation in nf l develop motor neuron disease lee et_amp_#xa0;al. 1994 . |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | nf l | 1.0 | removal of all axonal neurofilaments by deletion of nf l substantially prolonged survival of hsod1 g85r and hsod1 g37r mice nguyen et_amp_#xa0;al. 2001 and williamson et_amp_#xa0;al. 1998 as did removal of most axonal neurofilaments by excessive levels of |
| 7734 | NEFM | neurofilament, medium polypeptide 150kDa | nf m | 1.0 | this was demonstrated to be the case by use of gene replacement to remove the phosphorylated _amp_#x201c;tail_amp_#x201d; domains of nf m and nf h that normally provide intra axonal crosslinking of adjacent filaments. |
| 2711 | DCTN1 | dynactin 1 (p150, glued homolog, Drosophila) | p150 glued | 1.0 | additional evidence for a link between transport and motor neuron disease arose from the discovery of a mutation in the p150 glued subunit of dynactin in a family affected with a slowly progressive autosomal dominant form of lower motor neuron disease puls et_amp_#xa0;al. 2003 . p150 glued is responsible for providing processivi |
| 2711 | DCTN1 | dynactin 1 (p150, glued homolog, Drosophila) | p150 glued | 1.0 | subunit of dynactin in a family affected with a slowly progressive autosomal dominant form of lower motor neuron disease puls et_amp_#xa0;al. 2003 . p150 glued is responsible for providing processivity by bridging between microtubules and cytoplasmic dynein vaughan and vallee 1995 and waterman storer et_amp_#xa0;al. 1995 a motor powering retrograde axonal t |
| 15869 | KIF16B | kinesin family member 16B | kinesin motor protein | 1.0 | these include loss of the kinesin motor protein kif1b_amp_#x3b2; as causative for cmt type 2a zhao et_amp_#xa0;al. 2001 loss of kif5a in hereditary spastic paraplegia reid et_amp_#xa0;al. 2002 and loss of kif21a in a rare disorder affecting the oc |
| 7734 | NEFM | neurofilament, medium polypeptide 150kDa | nf m | 1.0 | hin neurons i.e. gene disruption to remove all neurofilaments [ williamson et_amp_#xa0;al. 1998 ] or gene replacement to alter axonal structure and volume after elimination of the tail domains of the nf m and nf h subunits [ lobsiger et_amp_#xa0;al. 2005 ] provide extended survival of sod1 mutant mice but only by slowing disease onset. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cyclooxygenase 2 cox 2 produced in abundance by microglia and other inflammatory cells but also by neurons and astrocytes plays a key role in stimulating production of proinflammatory cytokines and cox 2 expression is induced in spinal cords of als patients yasojima et_amp_#xa0;al. 2001 and yiangou et_amp_#xa0;al. 2006 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in mice use of a cox 2 inhibitor celecoxib prolonged survival by slowing disease onset drachman et_amp_#xa0;al. 2002 but disappointingly did not alter progression after onset. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor | 1.0 | one particularly interesting cytokine upregulated in mutant sod1 mouse spinal cords which could play a role in motor neuron degeneration is tumor necrosis factor _amp_#x3b1; tnf_amp_#x3b1; . |
| 11936 | FASLG | Fas ligand (TNF superfamily, member 6) | fas ligand | 1.0 | microglial cells could therefore be an important player in a fas ligand fasl induced apoptosis pathway within motor neurons that is driven by nitric oxide synthesis discussed in more detail below . |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | glt 1 | 1.0 | ential partners of motor neurons providing them with trophic support and mediating rapid recovery of synaptic glutamate through the action of the glial glutamate transporter eaat2 also referred to as glt 1 in rodents . |
| 4235 | GFAP | glial fibrillary acidic protein | glial fibrillary acidic protein | 1.0 | this includes an increase in assembly of their intermediate filaments assembled from glial fibrillary acidic protein gfap and an increase in the number and size of processes extended from the cell body figure_amp_#xa0;3 . |
| 4223 | MSTN | myostatin | myostatin | 1.0 | a test of whether enhanced muscle mass and strength per se can be beneficial in als has been attempted by repetitive injection into hsod1 g93a mice of an antibody to myostatin a secreted protein whose action inhibits muscle growth. |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | insulin like growth factor 1 | 1.0 | on the other hand muscle hypertrophy induced by agents such as insulin like growth factor 1 igf 1 or growth hormone dobrowolny et_amp_#xa0;al. 2005 kaspar et_amp_#xa0;al. 2003 and kaspar et_amp_#xa0;al. 2005 has led to significant life extensions in als transgenic mice. |
| 4232 | GDNF | glial cell derived neurotrophic factor | glial derived neurotrophic factor | 1.0 | a key improvement seems to be use of dibutyryl camp as an anti myelin repulsion factor and grafting of neural stem cells expressing glial derived neurotrophic factor gdnf into the nerve. |
| 7756 | NES | nestin | nestin | 1.0 | furthermore the endogenous recruitment of neural progenitors as determined by nestin staining was initiated on the predominantly symptomatic side of asymmetrically paralyzed hsod1 g93a rats de hemptinne et_amp_#xa0;al. 2006 . |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase 1 | 1.0 | superoxide dismutase 1|superoxide dismutase| |