)| PMID |
16624536 ( ) |
|---|---|
| Title | Innate immunity in amyotrophic lateral sclerosis. |
| Abstract | Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition in which motor neurons are selectively targeted. Although the underlying cause remains unclear, evidence suggests a role for innate immunity in disease pathogenesis. Neuroinflammation in areas of motor neuron loss is evident in presymptomatic mouse models of ALS and in human patients. Efforts aimed at attenuating the inflammatory response in ALS animal models have delayed symptom onset and extended survival. Seemingly conversely, attempts to sensitize cells of the innate immune system and modulate their phenotype have also shown efficacy. Effectors of innate immunity in the CNS appear to have ambivalent potential to promote either repair or injury. Because ALS is a syndromic disease in which glutamate excitotoxicity, altered cytoskeletal protein metabolism, oxidative injury, mitochondrial dysfunction and neuroinflammation all contribute to motor neuron degeneration, targeting inflammation via modulation of microglial function therefore holds significant potential as one aspect of therapeutic intervention and could provide insight into the exclusive vulnerability of motor neurons. Clinical Neurological Sciences, The University of Western Ontario, London, Ontario, Canada. |
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)) | 25 | superoxide dismutase 1 | SOD1 | |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | 18 | CSF-1 | M-CSF | colony stimulating factor 1 | macrophage colony stimulating factor | m csf | Csf1 | |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | 17 | IL-6 | il 6 | |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | 16 | COX | COX-2 | cox 2 | |
| 5992 | IL1B | interleukin 1, beta | 14 | IL-1 | il 1 | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 13 | TNF-expression | TNF-produced | TNF-dependant | |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | 10 | monocyte chemoattractant protein 1 | mcp 1 | MCP-1 | |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | 7 | Fas | Fas-associated | Fas-triggered | |
| 10647 | CX3CL1 | chemokine (C-X3-C motif) ligand 1 | 7 | fractalkine | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 6 | NOS | iNOS | nitric oxide synthase | |
| 5438 | IFNG | interferon, gamma | 6 | IFN- | IFN-G | interferon gamma | |
| 11916 | TNFRSF1A | tumor necrosis factor receptor superfamily, member 1A | 5 | TNFR1 | TNF-receptor | |
| 2434 | CSF2 | colony stimulating factor 2 (granulocyte-macrophage) | 5 | granulocyte macrophage colony stimulating factor | gm csf | GM-CSF | |
| 7808 | NGF | nerve growth factor (beta polypeptide) | 5 | nerve growth factor | NGF | |
| 11936 | FASLG | Fas ligand (TNF superfamily, member 6) | 4 | fas ligand | |
| 11917 | TNFRSF1B | tumor necrosis factor receptor superfamily, member 1B | 4 | p75-dependent | TNFR2 | |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 2 | Akt | protein kinase b | |
| 12030 | TRADD | TNFRSF1A-associated via death domain | 2 | TRADD | |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | 2 | Bcl-2 | bcl 2 | |
| 3665 | FGF1 | fibroblast growth factor 1 (acidic) | 2 | FGF-1 | fibroblast growth factor 1 | |
| 6011 | IL3 | interleukin 3 (colony-stimulating factor, multiple) | 2 | il 3 | IL-3 | |
| 992 | BCL2L1 | BCL2-like 1 | 2 | bcl xl | |
| 11848 | TLR2 | toll-like receptor 2 | 2 | toll like receptor 2 | TLR-2 | |
| 6709 | LTA | lymphotoxin alpha (TNF superfamily, member 1) | 2 | TNF-B | |
| 8053 | NUDT6 | nudix (nucleoside diphosphate linked moiety X)-type motif 6 | 2 | bFGF | |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | 2 | EAAT2 | |
| 6025 | IL8 | interleukin 8 | 2 | IL-8 | il 8 | |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | 1 | amyloid | |
| 19986 | CYCS | cytochrome c, somatic | 1 | cytochrome c | |
| 4931 | HLA-A | major histocompatibility complex, class I, A | 1 | MHC | |
| 9461 | PRPH | peripherin | 1 | peripherin | |
| 16462 | STRBP | spermatid perinuclear RNA binding protein | 1 | p74 | |
| 936 | BAD | BCL2-antagonist of cell death | 1 | BAD | |
| 991 | BCL2A1 | BCL2-related protein A1 | 1 | Bfl-1 | |
| 8020 | NT3 | 3'-nucleotidase | 1 | NT-3 | |
| 3689 | FGFR2 | fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) | 1 | fgf receptor | |
| 5991 | IL1A | interleukin 1, alpha | 1 | interleukin 1 | |
| 3688 | FGFR1 | fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, Pfeiffer syndrome) | 1 | FGFR1 | |
| 9071 | PLG | plasminogen | 1 | plasminogen | |
| 8975 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 1 | phosphatidylinositol 3 kinase | |
| 593 | BIRC5 | baculoviral IAP repeat-containing 5 (survivin) | 1 | survivin | |
| 4579 | GRIK1 | glutamate receptor, ionotropic, kainate 1 | 1 | mGluR5 | |
| 5997 | IL1RAPL2 | interleukin 1 receptor accessory protein-like 2 | 1 | il 1 receptor | |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | 1 | caspase 3 | |
| 6493 | LAMC2 | laminin, gamma 2 | 1 | CSFs | |
| 5993 | IL1R1 | interleukin 1 receptor, type I | 1 | Il-1ra | |
| 1509 | CASP8 | caspase 8, apoptosis-related cysteine peptidase | 1 | caspase 8 | |
| 2558 | CX3CR1 | chemokine (C-X3-C motif) receptor 1 | 1 | CX3CR1 | |
| 1876 | CFLAR | CASP8 and FADD-like apoptosis regulator | 1 | FLIP | |
| 5329 | IAPP | islet amyloid polypeptide | 1 | IAP | |
| 6130 | ISG20 | interferon stimulated exonuclease gene 20kDa | 1 | CD25 | |
| 1678 | CD4 | CD4 molecule | 1 | CD4 | |
| 591 | BIRC3 | baculoviral IAP repeat-containing 3 | 1 | inhibitor of apoptosis protein 1 | |
| 1033 | BDNF | brain-derived neurotrophic factor | 1 | BDNF | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | harbour missense mutations in the copper_amp_#x2013 zinc superoxide dismutase (SOD1) SOD1 gene 3 the majority of ALS cases are sporadic (sALS) |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 0.3 | astrocytes including interferon _amp_#x3b3 (IFN_amp_#x3b3;), IFN_amp_#x3b3 tumour necrosis factor (TNF TNF macrophage colony stimulating factor (M-CSF), M-CSF and granulocyte macrophage colony |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | M-CSF | 1.2 | tumour necrosis factor (TNF TNF macrophage colony stimulating factor (M-CSF), M-CSF and granulocyte macrophage colony stimulating factor (GM-CSF) GM-CSF |
| 2434 | CSF2 | colony stimulating factor 2 (granulocyte-macrophage) | GM-CSF | 2.2 | factor (M-CSF), M-CSF and granulocyte macrophage colony stimulating factor (GM-CSF) GM-CSF |
| 4931 | HLA-A | major histocompatibility complex, class I, A | MHC | 1.2 | In this state they express major histocompatibility (MHC) MHC class II molecules and present antigens |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | In response to secondary stimuli such as interleukin-1 (IL-1), IL-1 IL-6 and TNF- microglia exert maximal activity through secretion of |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.6 | In response to secondary stimuli such as interleukin-1 (IL-1), IL-1 IL-6 and TNF- microglia exert maximal activity through secretion of inflammatory |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF- | 0.3 | to secondary stimuli such as interleukin-1 (IL-1), IL-1 IL-6 and TNF- microglia exert maximal activity through secretion of inflammatory mediators ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | of motor neuron degeneration in which the fALS associated G93A SOD1 mutation is expressed is dependant on the extent of non-neuronal |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | recent work suggests the robust inflammatory response observed in symptomatic SOD1 G93A transgenic mice is mostly attributable to proliferation of resident |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | M-CSF | 1.2 | constitutively expressed in the human brain macrophage-colony stimulating factor (M-CSF) M-CSF receptor expression is upregulated in ALS precentral gyrus |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF- | 0.3 | Both TNF- and the soluble extracellular domains of its receptors TNFRI and |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.5 | An increased expression of pro-inflammatory cytokines COX-2 29 30 and 31 and of microglia-mediated protein oxidative pathology |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas | 0.6 | motor neuron death via TNF--mediated apoptotic mechanisms 35 and by Fas ligand or NO-induced apoptotic pathways 36 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | It has also been demonstrated that microglia derived from mutant SOD1 transgenic mice have increased cytotoxic potential in culture 37 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | Using a chimeric mutant SOD1 model in which only a proportion of cells express the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | model non-transgenic motor neurons surrounded by glia expressing the mutant SOD1 transgene degenerated while transgenic motor neurons surrounded by non-transgenic glia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | This study suggests that SOD1 mutations once thought to selectively confer motor neuron susceptibility can |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | from Don Cleveland's group suggesting that genetic knock-down of mutant SOD1 in cells of the macrophage lineage can significantly slow the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | neurons such as the skeletal muscle will also express mutant SOD1 and could contribute to the health of motor neurons |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | In contrast to these studies transgenic mice in which SOD1 G37R expression is driven by the mouse prion promoter resulting |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | by the mouse prion promoter resulting in levels of mutant SOD1 expression highest in neurons and astrocytes in the CNS and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | In both the mutant SOD1 transgenic mice and rat an alteration in the expression and |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | M-CSF | 1.2 | Specifically both TGF-_amp_#x3b2 1 and M-CSF expression are upregulated in presymptomatic mice with TNF-expression being increased |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-expression | 0.3 | 1 and M-CSF expression are upregulated in presymptomatic mice with TNF-expression being increased well in advance of the appearance of motor |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.5 | This process is associated with an increased level of COX-2 mRNA and protein and an increase in PGE 2 content |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.5 | excitotoxicity in organotypic spinal cord cultures can be suppressed by COX-2 inhibition 52 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | accelerated by chronic stimulation of inflammation using LPS in the SOD1 G37R mouse model of ALS with increasing levels of pro-inflammatory |
| 11848 | TLR2 | toll-like receptor 2 | TLR-2 | 1.6 | pro-inflammatory cytokines and increased expression of toll-like receptor 2 (TLR-2) TLR-2 53 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF- | 0.3 | induces neurotoxicity in primary cortical neurons via coincident stimulation of TNF- and NMDA receptors |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF- | 0.3 | Stimulation of either TNF- or NMDA receptors alone does not initiate cell death |
| 11916 | TNFRSF1A | tumor necrosis factor receptor superfamily, member 1A | TNF-receptor | 1.8 | Memantine and 2-amino-5-phosphopetanoic acid NMDA receptor antagonists and soluble TNF-receptor protect neurons from microglial-conditioned media-dependent death which is thought to |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.7 | from oxidative damage resulting from inducible nitric oxide synthase (iNOS) iNOS activity 59 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | Motor neurons derived from mutant SOD1 transgenic mice exhibit an increased susceptibility to activation of a |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas-triggered | 0.6 | transgenic mice exhibit an increased susceptibility to activation of a Fas-triggered cell death pathway that is unique to motor neurons and |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | NOS | 2.7 | neurons and which is dependent on transcriptional upregulation of neuronal NOS 36 |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas | 0.6 | explanation for the sensitivity of motor neurons in particular to Fas ligand and NO-triggered cell death mediated at least in part |
| 2434 | CSF2 | colony stimulating factor 2 (granulocyte-macrophage) | GM-CSF | 2.2 | the observation that granulocyte/macrophage granulocyte macrophage colony stimulating factor (GM-CSF) GM-CSF receptors are up-regulated on microglial cells adjacent to axotomized facial |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | CSF-1 | 1.2 | Colony stimulating factor-1 (CSF-1) CSF-1 promotes the proliferation and differentiation of both monocytes 64 and |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | Csf1 | 1.2 | In mice lacking this factor (Csf1 Csf1 op/op op op mutant mice only a limited microglial response |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | M-CSF | 1.2 | observed in mice in which macrophage colony stimulating factor (M-CSF) M-CSF is absent 67 |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.6 | IL-6 knockout mice not only fail to demonstrate the early microglial |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.6 | reduced astrocytic response in keeping with a dual role of IL-6 in both mediating motor neuron/microglial neuron microglial and microglial/astrocytic microglial |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | It is of interest that microglia derived from adult mutant SOD1 transgenic mice show decreased IL-6 production in response to LPS-stimulated |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.6 | microglia derived from adult mutant SOD1 transgenic mice show decreased IL-6 production in response to LPS-stimulated activation compared to controls 37 |
| 10647 | CX3CL1 | chemokine (C-X3-C motif) ligand 1 | fractalkine | 1.3 | The chemokine fractalkine has been identified as a chemoattractant in signaling the microglial |
| 10647 | CX3CL1 | chemokine (C-X3-C motif) ligand 1 | fractalkine | 1.3 | The fractalkine receptor CX3CR1 is expressed on both microglia and neurons 72 |
| 2558 | CX3CR1 | chemokine (C-X3-C motif) receptor 1 | CX3CR1 | 0.3 | The fractalkine receptor CX3CR1 is expressed on both microglia and neurons 72 |
| 10647 | CX3CL1 | chemokine (C-X3-C motif) ligand 1 | fractalkine | 1.3 | to a role in the migration and proliferation of microglia fractalkine may also function as a microglial activator as receptor expression |
| 10647 | CX3CL1 | chemokine (C-X3-C motif) ligand 1 | fractalkine | 1.3 | activation of the phosphatidylinositol-3 kinase/protein kinase protein kinase B pathway fractalkine will inhibit Fas ligand-induced microglial apoptosis through down-regulation of the |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas | 0.6 | phosphatidylinositol-3 kinase/protein kinase protein kinase B pathway fractalkine will inhibit Fas ligand-induced microglial apoptosis through down-regulation of the pro-apoptotic function of |
| 936 | BAD | BCL2-antagonist of cell death | BAD | 0.3 | ligand-induced microglial apoptosis through down-regulation of the pro-apoptotic function of BAD and up-regulation of the anti-apoptotic activity of Bcl XL 71 |
| 10647 | CX3CL1 | chemokine (C-X3-C motif) ligand 1 | fractalkine | 1.3 | A similar effect of fractalkine upon hippocampal neurons exposed to the HIV envelop protein gp120 |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.6 | been observed and attributed to activation of the protein kinase Akt and the nuclear translocation of NF-_amp_#x3ba B 72 and 75 |
| 10647 | CX3CL1 | chemokine (C-X3-C motif) ligand 1 | fractalkine | 1.3 | In murine cell culture experiments fractalkine suppressed the production of nitric oxide (NO), NO IL-6 and |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.6 | experiments fractalkine suppressed the production of nitric oxide (NO), NO IL-6 and TNF-by activated microglia and suppressed neuronal cell death induced |
| 5438 | IFNG | interferon, gamma | IFN-G | 0.6 | death induced by microglia activated with LPS and interferon-gamma (IFN-_amp_#x3b3;), IFN-_amp_#x3b3 in a dose-dependent manner |
| 10647 | CX3CL1 | chemokine (C-X3-C motif) ligand 1 | fractalkine | 1.3 | Thus fractalkine might function as an intrinsic inhibitor against activated microglial-induced neurotoxicity |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | neuron interactions include a number of pro-inflammatory cytokines (e.g., e.g. IL-1 IL-6 and TNF- 77 78 and 79 and neurotrophic factors |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.6 | interactions include a number of pro-inflammatory cytokines (e.g., e.g. IL-1 IL-6 and TNF- 77 78 and 79 and neurotrophic factors (e.g., |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF- | 0.3 | a number of pro-inflammatory cytokines (e.g., e.g. IL-1 IL-6 and TNF- 77 78 and 79 and neurotrophic factors (e.g., e.g. plasminogen |
| 8053 | NUDT6 | nudix (nucleoside diphosphate linked moiety X)-type motif 6 | bFGF | 1.0 | 78 and 79 and neurotrophic factors (e.g., e.g. plasminogen TGF-_amp_#x3b2 bFGF BDNF NGF NT-3 and NT-4 80 81 and 82 |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 0.3 | and 79 and neurotrophic factors (e.g., e.g. plasminogen TGF-_amp_#x3b2 bFGF BDNF NGF NT-3 and NT-4 80 81 and 82 |
| 7808 | NGF | nerve growth factor (beta polypeptide) | NGF | 1.2 | 79 and neurotrophic factors (e.g., e.g. plasminogen TGF-_amp_#x3b2 bFGF BDNF NGF NT-3 and NT-4 80 81 and 82 |
| 8020 | NT3 | 3'-nucleotidase | NT-3 | 0.3 | and neurotrophic factors (e.g., e.g. plasminogen TGF-_amp_#x3b2 bFGF BDNF NGF NT-3 and NT-4 80 81 and 82 |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | IL-1 and TNF-have similar biological properties in that at higher concentrations |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | IL-1 mediates a general inflammatory response that recruits the further secretion |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.6 | that recruits the further secretion of pro-inflammatory cytokines (e.g., e.g. IL-6 IL-8 colony stimulating factors (CSFs), CSFs IFN- _amp_#x3b2 and can |
| 6025 | IL8 | interleukin 8 | IL-8 | 1.3 | recruits the further secretion of pro-inflammatory cytokines (e.g., e.g. IL-6 IL-8 colony stimulating factors (CSFs), CSFs IFN- _amp_#x3b2 and can also |
| 6493 | LAMC2 | laminin, gamma 2 | CSFs | 0.3 | pro-inflammatory cytokines (e.g., e.g. IL-6 IL-8 colony stimulating factors (CSFs), CSFs IFN- _amp_#x3b2 and can also have a trophic effect |
| 5438 | IFNG | interferon, gamma | IFN- | 0.6 | cytokines (e.g., e.g. IL-6 IL-8 colony stimulating factors (CSFs), CSFs IFN- _amp_#x3b2 and can also have a trophic effect |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | The use of a recombinant IL-1 receptor antagonist (r-Hu-met r-Hu-met Il-1ra significantly reduces the volume of |
| 5993 | IL1R1 | interleukin 1 receptor, type I | Il-1ra | 0.3 | The use of a recombinant IL-1 receptor antagonist (r-Hu-met r-Hu-met Il-1ra significantly reduces the volume of damage following brain injury 84 |
| 7808 | NGF | nerve growth factor (beta polypeptide) | NGF | 1.2 | significant suppression of the extent of both microglial proliferation and NGF up-regulation is observed 85 |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | When IL-1 is added to mixed astrocytic/neuronal astrocytic neuronal cultures a 5- |
| 11916 | TNFRSF1A | tumor necrosis factor receptor superfamily, member 1A | TNFR1 | 1.8 | When signaling through the TNFR1 TNFR1 recruits a TNF receptor associated death domain (TRADD) TRADD |
| 11916 | TNFRSF1A | tumor necrosis factor receptor superfamily, member 1A | TNFR1 | 1.8 | When signaling through the TNFR1 TNFR1 recruits a TNF receptor associated death domain (TRADD) TRADD that |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 0.3 | When signaling through the TNFR1 TNFR1 recruits a TNF receptor associated death domain (TRADD) TRADD that can then interact |
| 12030 | TRADD | TNFRSF1A-associated via death domain | TRADD | 0.6 | TNFR1 TNFR1 recruits a TNF receptor associated death domain (TRADD) TRADD that can then interact with the Fas-associated death domain to |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas-associated | 0.6 | death domain (TRADD) TRADD that can then interact with the Fas-associated death domain to activate caspase 8 leading to downstream activation |
| 11916 | TNFRSF1A | tumor necrosis factor receptor superfamily, member 1A | TNFR1 | 1.8 | TNFR1 and TRADD activation can also lead to NF_amp_#x3ba B dependent |
| 12030 | TRADD | TNFRSF1A-associated via death domain | TRADD | 0.6 | TNFR1 and TRADD activation can also lead to NF_amp_#x3ba B dependent reporter gene |
| 5329 | IAPP | islet amyloid polypeptide | IAP | 0.3 | including survivin inhibitor of apoptosis protein-1 (IAP1), IAP1 IAP2 X-chromosome-linked IAP Bcl-2 Bcl-XL Bfl-1/A1, Bfl-1 A1 and FLIP 88 |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 1.0 | survivin inhibitor of apoptosis protein-1 (IAP1), IAP1 IAP2 X-chromosome-linked IAP Bcl-2 Bcl-XL Bfl-1/A1, Bfl-1 A1 and FLIP 88 |
| 1876 | CFLAR | CASP8 and FADD-like apoptosis regulator | FLIP | 1.0 | IAP1 IAP2 X-chromosome-linked IAP Bcl-2 Bcl-XL Bfl-1/A1, Bfl-1 A1 and FLIP 88 |
| 991 | BCL2A1 | BCL2-related protein A1 | Bfl-1 | 0.1 | apoptosis protein-1 (IAP1), IAP1 IAP2 X-chromosome-linked IAP Bcl-2 Bcl-XL Bfl-1/A1, Bfl-1 A1 and FLIP 88 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF- | 0.3 | The interaction of TNF- or TNF-_amp_#x3b2 with TNFR2 leads to the activation of NF-_amp_#x3ba |
| 6709 | LTA | lymphotoxin alpha (TNF superfamily, member 1) | TNF-B | 0.3 | The interaction of TNF- or TNF-_amp_#x3b2 with TNFR2 leads to the activation of NF-_amp_#x3ba B and |
| 11917 | TNFRSF1B | tumor necrosis factor receptor superfamily, member 1B | TNFR2 | 1.8 | The interaction of TNF- or TNF-_amp_#x3b2 with TNFR2 leads to the activation of NF-_amp_#x3ba B and the transcription |
| 11917 | TNFRSF1B | tumor necrosis factor receptor superfamily, member 1B | TNFR2 | 1.8 | Of interest knock out mice lacking TNFR2 show a failure to limit the immune response in experimental |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 0.3 | response in experimental autoimmune encephalitis and the use of p74 TNF receptor (TNFR2) TNFR2 antisense oligonucleotides will increase the extent of |
| 11917 | TNFRSF1B | tumor necrosis factor receptor superfamily, member 1B | TNFR2 | 1.8 | autoimmune encephalitis and the use of p74 TNF receptor (TNFR2) TNFR2 antisense oligonucleotides will increase the extent of a hypoxic injury |
| 16462 | STRBP | spermatid perinuclear RNA binding protein | p74 | 0.2 | immune response in experimental autoimmune encephalitis and the use of p74 TNF receptor (TNFR2) TNFR2 antisense oligonucleotides will increase the extent |
| 11916 | TNFRSF1A | tumor necrosis factor receptor superfamily, member 1A | TNF-receptor | 1.8 | of brain injury is increased in transgenic mice lacking the TNF-receptor 91 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-dependant | 0.3 | (an an NO-donor -induced neuronal apoptosis in vitro through a TNF-dependant mechanism whereas IL-3 IL-6 bFGF and M-CSF are ineffective in |
| 6011 | IL3 | interleukin 3 (colony-stimulating factor, multiple) | IL-3 | 1.6 | -induced neuronal apoptosis in vitro through a TNF-dependant mechanism whereas IL-3 IL-6 bFGF and M-CSF are ineffective in the same experimental |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.6 | neuronal apoptosis in vitro through a TNF-dependant mechanism whereas IL-3 IL-6 bFGF and M-CSF are ineffective in the same experimental paradigm |
| 8053 | NUDT6 | nudix (nucleoside diphosphate linked moiety X)-type motif 6 | bFGF | 1.0 | apoptosis in vitro through a TNF-dependant mechanism whereas IL-3 IL-6 bFGF and M-CSF are ineffective in the same experimental paradigm 92 |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | M-CSF | 1.2 | vitro through a TNF-dependant mechanism whereas IL-3 IL-6 bFGF and M-CSF are ineffective in the same experimental paradigm 92 |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 2.3 | Increased levels of monocyte chemoattractant protein-1 (MCP-1) MCP-1 are seen in the cerebrospinal fluid (CSF) CSF from ALS |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.3 | present antigen to Th1 cells which can in turn produce IL-1 IFN-_amp_#x3b3 TNF-_amp_#x3b2 and further activate macrophages |
| 5438 | IFNG | interferon, gamma | IFN-G | 0.6 | antigen to Th1 cells which can in turn produce IL-1 IFN-_amp_#x3b3 TNF-_amp_#x3b2 and further activate macrophages |
| 6709 | LTA | lymphotoxin alpha (TNF superfamily, member 1) | TNF-B | 0.3 | to Th1 cells which can in turn produce IL-1 IFN-_amp_#x3b3 TNF-_amp_#x3b2 and further activate macrophages |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | interest driving the adaptive immune response is protective against mutant SOD1 induced neurodegeneration |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | Vaccination of SOD1 G93A mice with Copaxone (copolymer-1) copolymer-1 led to an increase |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | Protection against _amp_#x3b2 -amyloid and glutamate excitotoxicity has been achieved through control of microglial |
| 1678 | CD4 | CD4 molecule | CD4 | 0.3 | control of microglial phenotype via the presence or absence of CD4 CD25 helper T cells 96 |
| 6130 | ISG20 | interferon stimulated exonuclease gene 20kDa | CD25 | 1.6 | of microglial phenotype via the presence or absence of CD4 CD25 helper T cells 96 |
| 5438 | IFNG | interferon, gamma | IFN-G | 0.6 | with CNS-specific self-antigens may arise from stimulation of microglia with IFN-_amp_#x3b3 which is produced by reactive helper T cells |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.5 | as well as decreased mRNA expression of inflammatory products including COX-2 iNOS and I_amp_#x3ba B (an an inhibitor of NF-_amp_#x3ba B |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.7 | well as decreased mRNA expression of inflammatory products including COX-2 iNOS and I_amp_#x3ba B (an an inhibitor of NF-_amp_#x3ba B by |
| 5438 | IFNG | interferon, gamma | IFN-G | 0.6 | In addition IFN-_amp_#x3b3 -stimulated microglia had greater antigen-presenting capability and were therefore able |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | Astrocytes isolated from a mutant SOD1 transgenic rat show a 3-fold higher expression of mGluR5 over |
| 4579 | GRIK1 | glutamate receptor, ionotropic, kainate 1 | mGluR5 | 0.3 | mutant SOD1 transgenic rat show a 3-fold higher expression of mGluR5 over controls activation of which fails to lead to increased |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | EAAT2 | 1.0 | been observed to have decreased expression of the glutamate transporter EAAT2 potentially leading to decreased glutamate transport and subsequent increases in |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | EAAT2 | 1.0 | this decrease in expression resulting from alternately spliced variants of EAAT2 has been demonstrated in normal controls in addition to ALS |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 2.3 | Monocyte chemoattractant protein-1 (MCP-1) MCP-1 is critical for migration of monoctyes to areas of injury |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 2.3 | discussed in relation to adaptive and acquired immunity in ALS MCP-1 concentrations are significantly increased in both serum and cerebrospinal fluid |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 2.3 | MCP-1 immunoreactivity is highest in astrocytes in ALS spinal cord suggesting |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.7 | Like microglia reactive astrocytes express inflammatory markers including iNOS and COX-2 114 and can produce proinflammatory mediators including prostaglandins |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.5 | Like microglia reactive astrocytes express inflammatory markers including iNOS and COX-2 114 and can produce proinflammatory mediators including prostaglandins 115 IL-6 |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.6 | COX-2 114 and can produce proinflammatory mediators including prostaglandins 115 IL-6 116 and TNF- 114 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF- | 0.3 | can produce proinflammatory mediators including prostaglandins 115 IL-6 116 and TNF- 114 |
| 3665 | FGF1 | fibroblast growth factor 1 (acidic) | FGF-1 | 1.2 | Fibroblast growth factor-1 (FGF-1) FGF-1 released from motor neurons in response to injury or oxidative |
| 3688 | FGFR1 | fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, Pfeiffer syndrome) | FGFR1 | 1.2 | or oxidative stress leads to accumulation of FGF receptor-1 (FGFR1) FGFR1 in astrocytic nuclei and stimulates nerve growth factor (NGF) NGF |
| 7808 | NGF | nerve growth factor (beta polypeptide) | NGF | 1.2 | FGFR1 in astrocytic nuclei and stimulates nerve growth factor (NGF) NGF expression and secretion by astrocytes 117 |
| 7808 | NGF | nerve growth factor (beta polypeptide) | NGF | 1.2 | This NGF production has been previously shown to induce motor neuron apoptosis |
| 11917 | TNFRSF1B | tumor necrosis factor receptor superfamily, member 1B | p75-dependent | 1.8 | been previously shown to induce motor neuron apoptosis via a p75-dependent mechanism 118 and 119 |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas | 0.6 | Fas ligand and TNF-produced by reactive astrocytes can also activate death |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-produced | 0.3 | Fas ligand and TNF-produced by reactive astrocytes can also activate death receptors in injured |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas | 0.6 | Raoul et al. ALS motor neurons are particularly susceptible to Fas signaling and the apoptotic pathway implicated is motor neuron-specific 36 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | of motor dysfunction by roughly 9_amp_#x2013 20% in various mutant SOD1 transgenic mice and extends survival by 13_amp_#x2013 25% (in in |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.7 | the level of the microglia in which the up-regulation of iNOS is inhibited and at the target cell where the release |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.5 | Celecoxib (Celebrex) Celebrex and rofecoxib are inhibitors of COX-2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.5 | Treatment with these COX-2 inhibitors combined with creatine increased survival by up to 30% |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | combined with creatine increased survival by up to 30% in SOD1 mutant mice 139 140 and 141 while treatment with a |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | mice 139 140 and 141 while treatment with a non-specific COX inhibitor (sulindac) sulindac extended survival by roughly 10% 142 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | should be noted however that to date none of the COX inhibitors tested have shown efficacy in human ALS patients |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | This is supported by evidence that mutant SOD1 secreted from neurons can activate microglia and lead to neuronal |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | The results of minocycline treatment of mutant SOD1 mice suggest that microglial activation is concomitant with and contributes |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | Although mutant SOD1 models allow for validation of potential treatments they do not |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | while between 5 and 8% of als cases are familial fals of which 20% harbour missense mutations in the copper_amp_#x2013;zinc superoxide dismutase sod1 gene [3] the majority of als cases are sporadic sals . |
| 9461 | PRPH | peripherin | peripherin | 1.0 | key components of the pathological process of als include glutamate excitotoxicity disturbances in cytoskeletal protein metabolism e.g. neurofilament peripherin oxidative injury altered mitochondrial function and neuroinflammation [5] and [6] . |
| 2434 | CSF2 | colony stimulating factor 2 (granulocyte-macrophage) | granulocyte macrophage colony stimulating factor | 1.0 | oglia become primed in response to primary stimuli from neurons or astrocytes including interferon _amp_#x3b3; ifn_amp_#x3b3; tumour necrosis factor tnf macrophage colony stimulating factor m csf and granulocyte macrophage colony stimulating factor gm csf . |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | macrophage colony stimulating factor | 1.0 | microglia become primed in response to primary stimuli from neurons or astrocytes including interferon _amp_#x3b3; ifn_amp_#x3b3; tumour necrosis factor tnf macrophage colony stimulating factor m csf and granulocyte macrophage colony stimulating factor gm csf . |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | macrophage colony stimulating factor | 1.0 | m csf and granulocyte macrophage colony stimulating factor gm csf . |
| 2434 | CSF2 | colony stimulating factor 2 (granulocyte-macrophage) | gm csf | 1.0 | i from neurons or astrocytes including interferon _amp_#x3b3; ifn_amp_#x3b3; tumour necrosis factor tnf macrophage colony stimulating factor m csf and granulocyte macrophage colony stimulating factor gm csf . |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | m csf | 1.0 | microglia become primed in response to primary stimuli from neurons or astrocytes including interferon _amp_#x3b3; ifn_amp_#x3b3; tumour necrosis factor tnf macrophage colony stimulating factor m csf and granulocyte macrophage colony stimulating factor gm csf . |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | in response to secondary stimuli such as interleukin 1 il 1 il 6 and tnf microglia exert maximal activity through secretion of inflammatory mediators fig 1 . |
| 5991 | IL1A | interleukin 1, alpha | interleukin 1 | 1.0 | in response to secondary stimuli such as interleukin 1 il 1 il 6 and tnf microglia exert maximal activity through secretion of inflammatory mediators fig 1 . |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | in response to secondary stimuli such as interleukin 1 il 1 il 6 and tnf microglia exert maximal activity through secretion of inflammatory mediators fig 1 . |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | macrophage colony stimulating factor | 1.0 | while constitutively expressed in the human brain macrophage colony stimulating factor m csf receptor expression is upregulated in als precentral gyrus. |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | m csf | 1.0 | while constitutively expressed in the human brain macrophage colony stimulating factor m csf receptor expression is upregulated in als precentral gyrus. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | an increased expression of pro inflammatory cytokines cox 2 [29] [30] and [31] and of microglia mediated protein oxidative pathology [32] is also observed in als. |
| 11936 | FASLG | Fas ligand (TNF superfamily, member 6) | fas ligand | 1.0 | in vitro experiments have shown that products released by activated microglia can lead to motor neuron death via tnf mediated apoptotic mechanisms [35] and by fas ligand or no induced apoptotic pathways [36] . |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | m csf | 1.0 | specifically both tgf _amp_#x3b2;1 and m csf expression are upregulated in presymptomatic mice with tnf expression being increased well in advance of the appearance of motor deficits. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | this process is associated with an increased level of cox 2 mrna and protein and an increase in pge 2 content limited to the regions associated with motor neuron pathology further confirming a role for microglial activation [31] and [51] . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the latter observation is consistent with in vitro observations that the motor neuron death induced by chronic glutamate excitotoxicity in organotypic spinal cord cultures can be suppressed by cox 2 inhibition [52] . |
| 11848 | TLR2 | toll-like receptor 2 | toll like receptor 2 | 1.0 | tor neuron disease is accelerated by chronic stimulation of inflammation using lps in the sod1 g37r mouse model of als with increasing levels of pro inflammatory cytokines and increased expression of toll like receptor 2 tlr 2 [53] . |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | oic acid nmda receptor antagonists and soluble tnf receptor protect neurons from microglial conditioned media dependent death which is thought to result from oxidative damage resulting from inducible nitric oxide synthase inos activity [59] . |
| 11936 | FASLG | Fas ligand (TNF superfamily, member 6) | fas ligand | 1.0 | this work may offer an explanation for the sensitivity of motor neurons in particular to fas ligand and no triggered cell death mediated at least in part by neighbouring microglia as trophic deprivation and excitotoxic stimulation did not have similar effects. |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | macrophage colony stimulating factor | 1.0 | this suggests a capacity for the motor neuron itself to _amp_#x201c;summon_amp_#x201d; a microglial response a postulate supported to some degree by the observation that granulocyte/macrophage colony stimulating factor gm csf receptors are up regulated on microglial cells adjacent to axotomized facial motor neurons [63] . |
| 2434 | CSF2 | colony stimulating factor 2 (granulocyte-macrophage) | gm csf | 1.0 | acity for the motor neuron itself to _amp_#x201c;summon_amp_#x201d; a microglial response a postulate supported to some degree by the observation that granulocyte/macrophage colony stimulating factor gm csf receptors are up regulated on microglial cells adjacent to axotomized facial motor neurons [63] . |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | colony stimulating factor 1 | 1.0 | colony stimulating factor 1 csf 1 promotes the proliferation and differentiation of both monocytes [64] and microglia [65] . |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | macrophage colony stimulating factor | 1.0 | following facial axotomy a similar loss of the early stages of microglial activation is observed in mice in which macrophage colony stimulating factor m csf is absent [67] . |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | m csf | 1.0 | following facial axotomy a similar loss of the early stages of microglial activation is observed in mice in which macrophage colony stimulating factor m csf is absent [67] . |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | il 6 knockout mice not only fail to demonstrate the early microglial response to motor neuron injury but also show a reduced astrocytic response in keeping with a dual role of il 6 in both mediating motor neuron/microglial and microglial/astrocytic interactions [68] . |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | it is of interest that microglia derived from adult mutant sod1 transgenic mice show decreased il 6 production in response to lps stimulated activation compared to controls [37] . |
| 8975 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | phosphatidylinositol 3 kinase | 1.0 | through activation of the phosphatidylinositol 3 kinase/protein kinase b pathway fractalkine will inhibit fas ligand induced microglial apoptosis through down regulation of the pro apoptotic function of bad and up regulation of the anti apoptotic activity |
| 992 | BCL2L1 | BCL2-like 1 | bcl xl | 1.0 | tein kinase b pathway fractalkine will inhibit fas ligand induced microglial apoptosis through down regulation of the pro apoptotic function of bad and up regulation of the anti apoptotic activity of bcl xl [71] thus promoting microglial cell survival. |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | protein kinase b | 1.0 | through activation of the phosphatidylinositol 3 kinase/protein kinase b pathway fractalkine will inhibit fas ligand induced microglial apoptosis through down regulation of the pro apoptotic function of bad and up regulation of the anti apoptotic activity of bcl xl [71] t |
| 11936 | FASLG | Fas ligand (TNF superfamily, member 6) | fas ligand | 1.0 | through activation of the phosphatidylinositol 3 kinase/protein kinase b pathway fractalkine will inhibit fas ligand induced microglial apoptosis through down regulation of the pro apoptotic function of bad and up regulation of the anti apoptotic activity of bcl xl [71] thus promoting microglial cell survival. |
| 5438 | IFNG | interferon, gamma | interferon gamma | 1.0 | ne cell culture experiments fractalkine suppressed the production of nitric oxide no il 6 and tnf by activated microglia and suppressed neuronal cell death induced by microglia activated with lps and interferon gamma ifn _amp_#x3b3; in a dose dependent manner. |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | in murine cell culture experiments fractalkine suppressed the production of nitric oxide no il 6 and tnf by activated microglia and suppressed neuronal cell death induced by microglia activated with lps and interferon gamma ifn _amp_#x3b3; in a dose dependent manner. |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | potential candidates for mediating microglia/motor neuron interactions include a number of pro inflammatory cytokines e.g. il 1 il 6 and tnf [77] [78] and [79] and neurotrophic factors e.g. plasminogen tgf _amp_#x3b2; bfgf bdnf ngf nt 3 and nt 4 [80] [81] and [82] . |
| 9071 | PLG | plasminogen | plasminogen | 1.0 | potential candidates for mediating microglia/motor neuron interactions include a number of pro inflammatory cytokines e.g. il 1 il 6 and tnf [77] [78] and [79] and neurotrophic factors e.g. plasminogen tgf _amp_#x3b2; bfgf bdnf ngf nt 3 and nt 4 [80] [81] and [82] . |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | potential candidates for mediating microglia/motor neuron interactions include a number of pro inflammatory cytokines e.g. il 1 il 6 and tnf [77] [78] and [79] and neurotrophic factors e.g. plasminogen tgf _amp_#x3b2; bfgf bdnf ngf nt 3 and nt 4 [80] [81] and [82] . |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | il 1 and tnf have similar biological properties in that at higher concentrations both mimic the cytotoxic effects of lps [83] . |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | il 1 mediates a general inflammatory response that recruits the further secretion of pro inflammatory cytokines e.g. il 6 il 8 colony stimulating factors csfs ifn /_amp_#x3b2; and can also have a trophic |
| 6025 | IL8 | interleukin 8 | il 8 | 1.0 | il 1 mediates a general inflammatory response that recruits the further secretion of pro inflammatory cytokines e.g. il 6 il 8 colony stimulating factors csfs ifn /_amp_#x3b2; and can also have a trophic effect. |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | il 1 mediates a general inflammatory response that recruits the further secretion of pro inflammatory cytokines e.g. il 6 il 8 colony stimulating factors csfs ifn /_amp_#x3b2; and can also have a trophic effect. |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | the use of a recombinant il 1 receptor antagonist r hu met il 1ra significantly reduces the volume of damage following brain injury [84] . |
| 5997 | IL1RAPL2 | interleukin 1 receptor accessory protein-like 2 | il 1 receptor | 1.0 | the use of a recombinant il 1 receptor antagonist r hu met il 1ra significantly reduces the volume of damage following brain injury [84] . |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | when il 1 is added to mixed astrocytic/neuronal cultures a 5 to 7 fold increase in astrocytes is observed [86] . |
| 1509 | CASP8 | caspase 8, apoptosis-related cysteine peptidase | caspase 8 | 1.0 | when signaling through the tnfr1 tnfr1 recruits a tnf receptor associated death domain tradd that can then interact with the fas associated death domain to activate caspase 8 leading to downstream activation of effector caspases. |
| 593 | BIRC5 | baculoviral IAP repeat-containing 5 (survivin) | survivin | 1.0 | tnfr1 and tradd activation can also lead to nf_amp_#x3ba;b dependent reporter gene expression that in turn drives expression of anti apoptotic gene products including survivin inhibitor of apoptosis protein 1 iap1 iap2 x chromosome linked iap bcl 2 bcl xl bfl 1/a1 and flip [88] . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | nf_amp_#x3ba;b dependent reporter gene expression that in turn drives expression of anti apoptotic gene products including survivin inhibitor of apoptosis protein 1 iap1 iap2 x chromosome linked iap bcl 2 bcl xl bfl 1/a1 and flip [88] . |
| 992 | BCL2L1 | BCL2-like 1 | bcl xl | 1.0 | p_#x3ba;b dependent reporter gene expression that in turn drives expression of anti apoptotic gene products including survivin inhibitor of apoptosis protein 1 iap1 iap2 x chromosome linked iap bcl 2 bcl xl bfl 1/a1 and flip [88] . |
| 591 | BIRC3 | baculoviral IAP repeat-containing 3 | inhibitor of apoptosis protein 1 | 1.0 | tnfr1 and tradd activation can also lead to nf_amp_#x3ba;b dependent reporter gene expression that in turn drives expression of anti apoptotic gene products including survivin inhibitor of apoptosis protein 1 iap1 iap2 x chromosome linked iap bcl 2 bcl xl bfl 1/a1 and flip [88] . |
| 6011 | IL3 | interleukin 3 (colony-stimulating factor, multiple) | il 3 | 1.0 | microglia can also inhibit sodium nitroprusside an no donor induced neuronal apoptosis in vitro through a tnf dependant mechanism whereas il 3 il 6 bfgf and m csf are ineffective in the same experimental paradigm [92] . |
| 2432 | CSF1 | colony stimulating factor 1 (macrophage) | m csf | 1.0 | microglia can also inhibit sodium nitroprusside an no donor induced neuronal apoptosis in vitro through a tnf dependant mechanism whereas il 3 il 6 bfgf and m csf are ineffective in the same experimental paradigm [92] . |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | microglia can also inhibit sodium nitroprusside an no donor induced neuronal apoptosis in vitro through a tnf dependant mechanism whereas il 3 il 6 bfgf and m csf are ineffective in the same experimental paradigm [92] . |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | increased levels of monocyte chemoattractant protein 1 mcp 1 are seen in the cerebrospinal fluid csf from als patients [98] and [99] . |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | monocyte chemoattractant protein 1 | 1.0 | increased levels of monocyte chemoattractant protein 1 mcp 1 are seen in the cerebrospinal fluid csf from als patients [98] and [99] . |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | these cells present antigen to th1 cells which can in turn produce il 1 ifn _amp_#x3b3; tnf _amp_#x3b2; and further activate macrophages. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | this stimulation results in increased glutamate uptake and decreased no production as well as decreased mrna expression of inflammatory products including cox 2 inos and i_amp_#x3ba;b an inhibitor of nf _amp_#x3ba;b by microglia compared to lps treated microglia. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | an in vitro experiment demonstrated in mixed primary spinal cord cultures that igg from patients with als induces apoptosis via the caspase 3 pathway selectively in motor neurons [107] . |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | monocyte chemoattractant protein 1 mcp 1 is critical for migration of monoctyes to areas of injury. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | monocyte chemoattractant protein 1 | 1.0 | monocyte chemoattractant protein 1 mcp 1 is critical for migration of monoctyes to areas of injury. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | as discussed in relation to adaptive and acquired immunity in als mcp 1 concentrations are significantly increased in both serum and cerebrospinal fluid csf from als patients. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | mcp 1 immunoreactivity is highest in astrocytes in als spinal cord suggesting that astrocytes have an important role in mediating the inflammatory response to injury in als [98] . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | like microglia reactive astrocytes express inflammatory markers including inos and cox 2 [114] and can produce proinflammatory mediators including prostaglandins [115] il 6 [116] and tnf [114] . |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | like microglia reactive astrocytes express inflammatory markers including inos and cox 2 [114] and can produce proinflammatory mediators including prostaglandins [115] il 6 [116] and tnf [114] . |
| 7808 | NGF | nerve growth factor (beta polypeptide) | nerve growth factor | 1.0 | fibroblast growth factor 1 fgf 1 released from motor neurons in response to injury or oxidative stress leads to accumulation of fgf receptor 1 fgfr1 in astrocytic nuclei and stimulates nerve growth factor ngf expression and secretion by astrocytes [117] . |
| 3665 | FGF1 | fibroblast growth factor 1 (acidic) | fibroblast growth factor 1 | 1.0 | fibroblast growth factor 1 fgf 1 released from motor neurons in response to injury or oxidative stress leads to accumulation of fgf receptor 1 fgfr1 in astrocytic nuclei and stimulates nerve growth factor ngf expression and se |
| 3689 | FGFR2 | fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) | fgf receptor | 1.0 | fibroblast growth factor 1 fgf 1 released from motor neurons in response to injury or oxidative stress leads to accumulation of fgf receptor 1 fgfr1 in astrocytic nuclei and stimulates nerve growth factor ngf expression and secretion by astrocytes [117] . |
| 11936 | FASLG | Fas ligand (TNF superfamily, member 6) | fas ligand | 1.0 | fas ligand and tnf produced by reactive astrocytes can also activate death receptors in injured motor neurons. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | the site of action of minocycline appears to be at both the level of the microglia in which the up regulation of inos is inhibited and at the target cell where the release of mitochondrial cytochrome c and thus the initiation of a pro apoptotic pathway is inhibited [127] [128] [129] and [130] . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | celecoxib celebrex and rofecoxib are inhibitors of cox 2. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | treatment with these cox 2 inhibitors combined with creatine increased survival by up to 30% in sod1 mutant mice [139] [140] and [141] while treatment with a non specific cox inhibitor sulindac extended survival by roughly 10% |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase 1 | 1.0 | superoxide dismutase 1|superoxide dismutase| |