)| PMID |
17582695 ( ) |
|---|---|
| Title | Are multiple sclerosis and amyotrophic lateral sclerosis autoimmune disorders of endogenous vasoactive neuropeptides? |
| Abstract | Autoimmune dysfunction of endogenous vasoactive neuropeptides (VNs) such as vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) has been postulated as a cause for some fatigue-related conditions. VN receptors are class II G protein-coupled receptors (GPCRs) which couple primarily to the adenylate cyclase (AC)-cyclic AMP (cAMP) pathway and cAMP has a central role in neurological metabolism including influencing blood-brain barrier (BBB) and blood-spinal barrier (BSB) permeability, coordinating neuroregulatory pathways, and protecting against neuronal apoptosis. Complex clinical signs occur in multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While traditionally viewed as diseases of the motor system, the clinical picture of these conditions is considerably more complex. Disturbances of cognition and memory, as well as emotional lability occur along with fatigue and motor dysfunction. This paper explores the hypothesis that autoimmune dysfunction of VNs may contribute to MS and ALS. While MS and ALS differ in important respects, they have common pathogenic features including inflammation, oxidative stress and mitochondrial dysfunction. Apoptotic mechanisms are associated with activation of caspase pathways and functional interplay between proinflammatory cytokines, interferon gamma and nitric oxide is suggested associated with oxidative stress and glial activation. Diseases such as MS and ALS may represent related conditions resulting from variation in expression of different receptor subtypes of the VN family. Anatomical differences of these receptors, perhaps in areas overly dependent on a specific VN receptor sub-type, may predispose to autoimmune susceptibility to these conditions, either in impaired expression of receptors or antibody and cellular immune targeting of them. Further studies are required to determine if such VN receptor sub-types of significant specificity exist and if they are susceptible to compromise. This hypothesis, if proven, may have implications for the development of treatment and preventive strategies. Queensland, Australia. don_staines@health.qld.gov.au <don_staines@health.qld.gov.au> |
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 |
|---|---|---|---|---|
| 241 | ADCYAP1 | adenylate cyclase activating polypeptide 1 (pituitary) | 11 | adenylate cyclase activating polypeptide | PACAP | |
| 12693 | VIP | vasoactive intestinal peptide | 9 | vasoactive intestinal peptide | VIP | |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | 6 | MAPK | p38 | |
| 12680 | VEGFA | vascular endothelial growth factor A | 5 | VEGF | vascular endothelial growth factor | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 5 | TNFalpha | tnf alpha | TNF | |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | 2 | HSPs | |
| 3415 | EPO | erythropoietin | 2 | EPO | erythropoietin | |
| 12695 | VIPR2 | vasoactive intestinal peptide receptor 2 | 2 | VPAC2 | |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | 2 | IL-6 | il 6 | |
| 4910 | HIF1A | hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) | 2 | HIF-1 | hypoxia inducible factor 1 | |
| 5962 | IL10 | interleukin 10 | 2 | IL-10 | il 10 | |
| 5438 | IFNG | interferon, gamma | 2 | interferon gamma | |
| 5992 | IL1B | interleukin 1, beta | 2 | IL-1beta | |
| 4232 | GDNF | glial cell derived neurotrophic factor | 2 | GDNF | glial cell line derived neurotrophic factor | |
| 21285 | ADCY10 | adenylate cyclase 10 (soluble) | 2 | adenylate cyclase | |
| 108 | ACHE | acetylcholinesterase (Yt blood group) | 1 | acetylcholinesterase | |
| 6876 | MAPK14 | mitogen-activated protein kinase 14 | 1 | p38 mitogen activated protein kinase | |
| 11848 | TLR2 | toll-like receptor 2 | 1 | toll like receptor 2 | |
| 18420 | SETD2 | SET domain containing 2 | 1 | hif 1 | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 1 | SOD1 | |
| 12694 | VIPR1 | vasoactive intestinal peptide receptor 1 | 1 | vip receptor | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 12693 | VIP | vasoactive intestinal peptide | VIP | 2.2 | vasoactive neuropeptides (VNs) VNs such as vasoactive intestinal peptide (VIP) VIP and pituitary adenylate cyclase activating polypeptide (PACAP) PACAP has been |
| 241 | ADCYAP1 | adenylate cyclase activating polypeptide 1 (pituitary) | PACAP | 3.3 | peptide (VIP) VIP and pituitary adenylate cyclase activating polypeptide (PACAP) PACAP has been postulated as a cause for some fatigue-related conditions |
| 12693 | VIP | vasoactive intestinal peptide | VIP | 2.2 | vasoactive neuropeptides (VNs) VNs such as vasoactive intestinal peptide (VIP) VIP and pituitary adenylate cyclase activating polypeptide (PACAP) PACAP has been |
| 241 | ADCYAP1 | adenylate cyclase activating polypeptide 1 (pituitary) | PACAP | 3.3 | peptide (VIP) VIP and pituitary adenylate cyclase activating polypeptide (PACAP) PACAP has been postulated as a cause for some fatigue-related conditions |
| 241 | ADCYAP1 | adenylate cyclase activating polypeptide 1 (pituitary) | PACAP | 3.3 | Interestingly PACAP protects against Rotenone neuronal injury 8 and 9 hence autoimmune |
| 241 | ADCYAP1 | adenylate cyclase activating polypeptide 1 (pituitary) | PACAP | 3.3 | Rotenone neuronal injury 8 and 9 hence autoimmune compromise of PACAP may have predisposed to neuronal pathology of Parkinson_amp_#x2019 s or |
| 5962 | IL10 | interleukin 10 | IL-10 | 1.0 | 1 25-dihydroxyvitamin D(3) D 3 may protect against MS via IL-10 11 a cytokine associated with VN activity in inflammatory contexts |
| 4910 | HIF1A | hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) | HIF-1 | 0.6 | IL-1beta and hypoxia inducible factor-1 (HIF-1) HIF-1 play important roles in influencing vessel plasticity along with vascular |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 2.8 | influencing vessel plasticity along with vascular endothelial growth factor (VEGF) VEGF 22 |
| 5992 | IL1B | interleukin 1, beta | IL-1beta | 0.0 | IL-1beta and hypoxia inducible factor-1 (HIF-1) HIF-1 play important roles in |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 2.8 | Serum VEGF is higher in ALS in human samples than controls 23 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 2.8 | samples than controls 23 as it is in MS where VEGF shows a correlation with length of spinal cord lesions 24 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 0.5 | cortex and brainstem although not in spinal cord of transgenic SOD1 (G93A) G93A mice models of ALS 25 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 2.8 | High erythropoietin and low VEGF in CSF from hypoxemic ALS patients suggest an abnormal response |
| 3415 | EPO | erythropoietin | EPO | 1.0 | Moreover low concentrations of EPO in CSF point to a rapid progression of disease that |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.3 | neurodegenerative disorders such as ALS and PD e.g. IL-1beta and IL-6 32 |
| 5992 | IL1B | interleukin 1, beta | IL-1beta | 0.1 | cytokines in neurodegenerative disorders such as ALS and PD e.g. IL-1beta and IL-6 32 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p38 | 1.7 | The p38 mitogen-activated protein kinase (p38MAPK) p38MAPK is activated by a variety |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p38 | 1.7 | Inhibition of p38 signalling activated by NO exposure in rat models of MS |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p38 | 1.7 | Activation of p38 MAPK is associated with upregulation of TNF alpha receptors in |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 1.7 | Activation of p38 MAPK is associated with upregulation of TNF alpha receptors in the |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 1.0 | Activation of p38 MAPK is associated with upregulation of TNF alpha receptors in the spinal motor neurons of mouse models |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 1.0 | Thus TNF alpha signalling is postulated to have a key role in |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p38 | 1.7 | Importantly p38 MAPK pathway is selectively inhibited by PACAP in hypoxic activation |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 1.7 | Importantly p38 MAPK pathway is selectively inhibited by PACAP in hypoxic activation of |
| 241 | ADCYAP1 | adenylate cyclase activating polypeptide 1 (pituitary) | PACAP | 3.3 | Importantly p38 MAPK pathway is selectively inhibited by PACAP in hypoxic activation of microglial cells 40 suggesting neuroprotection in |
| 241 | ADCYAP1 | adenylate cyclase activating polypeptide 1 (pituitary) | PACAP | 3.3 | Moreover PACAP exerts this protective effect in endothelial cells protecting them against |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNFalpha | 1.0 | Modest increases in multiple synergistic cytokines including TNFalpha TGFbeta1 and TGFbeta2 may produce a disproportionately severe activation of |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | HSPs | 0.9 | their association with variable levels of heat shock proteins (HSPs) HSPs 50 |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | HSPs | 0.9 | HSPs may have a role in postulated VN autoimmune disorders 51 |
| 12693 | VIP | vasoactive intestinal peptide | VIP | 2.2 | however in a series of ALS patients CSF levels of VIP were found to be significantly lower compared with controls 52 |
| 12693 | VIP | vasoactive intestinal peptide | VIP | 2.2 | VIP has demonstrated potent effects on neurite outgrowth in spinal cord |
| 12693 | VIP | vasoactive intestinal peptide | VIP | 2.2 | Interestingly Sun et al 54 noted impaired VIP receptor (VPAC2) VPAC2 production in activated T cells in MS |
| 12695 | VIPR2 | vasoactive intestinal peptide receptor 2 | VPAC2 | 3.0 | Interestingly Sun et al 54 noted impaired VIP receptor (VPAC2) VPAC2 production in activated T cells in MS patients suggesting transcription |
| 12695 | VIPR2 | vasoactive intestinal peptide receptor 2 | VPAC2 | 3.0 | MS patients suggesting transcription irregularity at promoter regions of the VPAC2 gene |
| 12693 | VIP | vasoactive intestinal peptide | VIP | 2.2 | finding may be extremely important as more widespread impairment of VIP if proven in patients with MS may explain the complete |
| 241 | ADCYAP1 | adenylate cyclase activating polypeptide 1 (pituitary) | PACAP | 3.3 | Moreover PACAP expression in the ventral horn of the spinal cord is |
| 241 | ADCYAP1 | adenylate cyclase activating polypeptide 1 (pituitary) | PACAP | 3.3 | in response to sciatic nerve transection suggesting a role for PACAP in repair or regeneration of motor neurons 57 |
| 12693 | VIP | vasoactive intestinal peptide | VIP | 2.2 | Similarly VIP may have a role in MS treatment 58 |
| 4232 | GDNF | glial cell derived neurotrophic factor | GDNF | 1.2 | cells may involve glial cell line derived neurotrophic factor (GDNF) GDNF around host motor neurons produced by grafted cells 68 |
| 241 | ADCYAP1 | adenylate cyclase activating polypeptide 1 (pituitary) | adenylate cyclase activating polypeptide | 1.0 | autoimmune dysfunction of endogenous vasoactive neuropeptides vns such as vasoactive intestinal peptide vip and pituitary adenylate cyclase activating polypeptide pacap has been postulated as a cause for some fatigue related conditions. |
| 12693 | VIP | vasoactive intestinal peptide | vasoactive intestinal peptide | 1.0 | autoimmune dysfunction of endogenous vasoactive neuropeptides vns such as vasoactive intestinal peptide vip and pituitary adenylate cyclase activating polypeptide pacap has been postulated as a cause for some fatigue related conditions. |
| 21285 | ADCY10 | adenylate cyclase 10 (soluble) | adenylate cyclase | 1.0 | vn receptors are class ii g protein coupled receptors gpcrs which couple primarily to the adenylate cyclase ac cyclic amp camp pathway and camp has a central role in neurological metabolism including influencing blood brain barrier bbb and blood spinal barrier bsb permeability coordinating neuroregulatory |
| 5438 | IFNG | interferon, gamma | interferon gamma | 1.0 | apoptotic mechanisms are associated with activation of caspase pathways and functional interplay between proinflammatory cytokines interferon gamma and nitric oxide is suggested associated with oxidative stress and glial activation. |
| 241 | ADCYAP1 | adenylate cyclase activating polypeptide 1 (pituitary) | adenylate cyclase activating polypeptide | 1.0 | autoimmune dysfunction of endogenous vasoactive neuropeptides vns such as vasoactive intestinal peptide vip and pituitary adenylate cyclase activating polypeptide pacap has been postulated as a cause for some fatigue related conditions. |
| 12693 | VIP | vasoactive intestinal peptide | vasoactive intestinal peptide | 1.0 | autoimmune dysfunction of endogenous vasoactive neuropeptides vns such as vasoactive intestinal peptide vip and pituitary adenylate cyclase activating polypeptide pacap has been postulated as a cause for some fatigue related conditions. |
| 21285 | ADCY10 | adenylate cyclase 10 (soluble) | adenylate cyclase | 1.0 | vn receptors are class ii g protein coupled receptors gpcrs which couple primarily to the adenylate cyclase ac cyclic amp pathway [2] . |
| 5962 | IL10 | interleukin 10 | il 10 | 1.0 | importantly vitamin d 3 and 1 25 dihydroxyvitamin d 3 may protect against ms via il 10 [11] a cytokine associated with vn activity in inflammatory contexts [12] . |
| 4910 | HIF1A | hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) | hypoxia inducible factor 1 | 1.0 | il 1beta and hypoxia inducible factor 1 hif 1 play important roles in influencing vessel plasticity along with vascular endothelial growth factor vegf [22] . |
| 18420 | SETD2 | SET domain containing 2 | hif 1 | 1.0 | il 1beta and hypoxia inducible factor 1 hif 1 play important roles in influencing vessel plasticity along with vascular endothelial growth factor vegf [22] . |
| 12680 | VEGFA | vascular endothelial growth factor A | vascular endothelial growth factor | 1.0 | il 1beta and hypoxia inducible factor 1 hif 1 play important roles in influencing vessel plasticity along with vascular endothelial growth factor vegf [22] . |
| 3415 | EPO | erythropoietin | erythropoietin | 1.0 | high erythropoietin and low vegf in csf from hypoxemic als patients suggest an abnormal response to hypoxia compared with hypoxic controls [26] . |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | biochemical mediators such as glutamate are modulated by certain cytokines in neurodegenerative disorders such as als and pd e.g. il 1beta and il 6 [32] . |
| 5438 | IFNG | interferon, gamma | interferon gamma | 1.0 | apoptotic mechanisms are associated with activation of caspase pathways and functional interplay between proinflammatory cytokines interferon gamma and nitric oxide is suggested associated with oxidative stress and glial activation in als [33] . |
| 6876 | MAPK14 | mitogen-activated protein kinase 14 | p38 mitogen activated protein kinase | 1.0 | the p38 mitogen activated protein kinase p38mapk is activated by a variety of stimuli including oxidative stress excitotoxicity and inflammatory cytokines. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | activation of p38 mapk is associated with upregulation of tnf alpha receptors in the spinal motor neurons of mouse models of familial als [38] . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | thus tnf alpha signalling is postulated to have a key role in als [39] . |
| 11848 | TLR2 | toll-like receptor 2 | toll like receptor 2 | 1.0 | innate immune receptor toll like receptor 2 and proinflammatory cytokines are implicated in a lipopolysaccharide model of als suggesting that environmental factors and innate immunity are linked [42] . |
| 12694 | VIPR1 | vasoactive intestinal peptide receptor 1 | vip receptor | 1.0 | interestingly sun et al. [54] noted impaired vip receptor vpac2 production in activated t cells in ms patients suggesting transcription irregularity at promoter regions of the vpac2 gene. |
| 108 | ACHE | acetylcholinesterase (Yt blood group) | acetylcholinesterase | 1.0 | the use of selective acetylcholinesterase inhibitors in ms and eae [63] and [64] would also be consistent with postulated vn autoimmunity [65] . |
| 4232 | GDNF | glial cell derived neurotrophic factor | glial cell line derived neurotrophic factor | 1.0 | therapies aimed at haematopoietic stem cells may involve glial cell line derived neurotrophic factor gdnf around host motor neurons produced by grafted cells [68] . |
| 241 | ADCYAP1 | adenylate cyclase activating polypeptide 1 (pituitary) | adenylate cyclase activating polypeptide | 1.0 | adcyap1 protein human|neuropeptides|pituitary adenylate cyclase activating polypeptide|receptors g protein coupled|vasoactive intestinal peptide| |