)| PMID |
14556941 ( ) |
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| Title | Riluzole suppresses experimental autoimmune encephalomyelitis: implications for the treatment of multiple sclerosis. |
| Abstract | Recent studies suggest that glutamate neurotoxicity is involved in the pathogenesis of multiple sclerosis (MS), and that treatment with glutamate receptor (AMPA/kainate) antagonists inhibits experimental autoimmune encephalomyelitis (EAE), the conventional model of MS. Therefore, we examined whether riluzole, an inhibitor of glutamate transmission, affects the pathogenesis and clinical features of MS-like disease in myelin oligodendrocyte glycoprotein (MOG)-induced EAE in mice. Here we report that riluzole (10 mg/kgx2/day, i.p.), administered before and even after the appearance of clinical symptoms, dramatically reduced the clinical severity of MOG-induced EAE, while all the MOG-immunized control mice developed significant clinical manifestations. Moreover, the riluzole-treated mice demonstrated only mild focal inflammation, and less demyelination, compared to MOG-treated mice, using histological methods. Furthermore, riluzole markedly reduced axonal disruption, as assessed by Bielshowesky's silver staining and by antibodies against non-phosphorylated neurofilaments (SMI-32). No difference was detected in the immune system potency, as T-cell proliferative responses to MOG were similar in both groups. In conclusion, our study demonstrates, for the first time, that riluzole can reduce inflammation, demyelination and axonal damage in the CNS and attenuate the clinical severity of MOG-induced EAE. These results suggest that riluzole, a drug used in amyotrophic lateral sclerosis (ALS), might be beneficial for the treatment of MS. Department of Neurology, Rabin Medical Center-Beilinson Campus, The Sackler School of Medicine, Tel Aviv University, Petah Tikva 49100, Israel. |
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 |
|---|---|---|---|---|
| 7197 | MOG | myelin oligodendrocyte glycoprotein | 35 | MOG-immunized | MOG-induced | MOG-treated | myelin oligodendrocyte glycoprotein | |
| 4571 | GRIA1 | glutamate receptor, ionotropic, AMPA 1 | 3 | glutamate receptor | |
| 7737 | NEFH | neurofilament, heavy polypeptide 200kDa | 2 | NF-H | |
| 4341 | GLUL | glutamate-ammonia ligase (glutamine synthetase) | 1 | glutamine synthetase | |
| 6783 | MAG | myelin associated glycoprotein | 1 | myelin associated glycoprotein | |
| 6925 | MBP | myelin basic protein | 1 | myelin basic protein | |
| 4573 | GRIA3 | glutamate receptor, ionotrophic, AMPA 3 | 1 | GluR3 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG | 1.9 | clinical features of MS-like disease in myelin oligodendrocyte glycoprotein (MOG)-induced MOG -induced EAE in mice |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-induced | 1.9 | appearance of clinical symptoms dramatically reduced the clinical severity of MOG-induced EAE while all the MOG-immunized control mice developed significant clinical |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-immunized | 1.9 | reduced the clinical severity of MOG-induced EAE while all the MOG-immunized control mice developed significant clinical manifestations |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-treated | 1.9 | demonstrated only mild focal inflammation and less demyelination compared to MOG-treated mice using histological methods |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG | 1.9 | in the immune system potency as T-cell proliferative responses to MOG were similar in both groups |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-induced | 1.9 | damage in the CNS and attenuate the clinical severity of MOG-induced EAE |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG | 1.9 | insult to neurons and axons in myelin oligodendrocyte glycoprotein (MOG)-induced MOG -induced EAE in C3H.SW mice a chronic model which appears |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG | 1.9 | with the peptide encompassing amino acids 35_amp_#x2013 55 of rat MOG |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG | 1.9 | with a 200 _amp_#x3bc l emulsion containing 75 _amp_#x3bc g MOG peptide (300 300 _amp_#x3bc g in the case of C57/bl) |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG | 1.9 | Spinal cords from riluzole-treated and MOG mice were dissected 28 days after immunization with pMOG 35_amp_#x2013 |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG- | 1.9 | severity of EAE following pMOG 35_amp_#x2013 55 induction between the MOG- and riluzole-treated mice groups was evaluated using Student_amp_#x2019 s t |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG | 1.9 | when it was administered together with the first injection of MOG was shown to be beneficial in reducing clinical symptoms ( |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG | 1.9 | twice a day was given 14 days after the first MOG injection at the appearance of symptoms |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG | 1.9 | riluzole-treated mice ( n =10 as measured 30 days after MOG injection was much lower than for the MOG-treated mice (1.18_amp_#xb1;0.47 |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-treated | 1.9 | days after MOG injection was much lower than for the MOG-treated mice (1.18_amp_#xb1;0.47 1.18_amp_#xb1 0.47 vs 2.31_amp_#xb1 0.23 P _amp_#x3c 0.03 |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG | 1.9 | Twenty-seven days after MOG injection there were marked differences between the control (CC) CC |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-induced | 1.9 | of the 10 riluzole-treated (RR) RR mice remained resistant to MOG-induced EAE and remained disease free ( P =0.001 using _amp_#x3c7 |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG | 1.9 | Representative H_amp_#x26 E staining of spinal cords from five immunized MOG mice 28 days after immunization revealed marked multifocal lymphohistiocytic inflammation |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-treated | 1.9 | in the number of lymphocytes in the spinal cord of MOG-treated mice compared to naive mice as indicated by arbitrary units |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-treated | 1.9 | was dramatically reduced in riluzole-treated mice as compared to the MOG-treated group (0.036_amp_#xb1;0.007 0.036_amp_#xb1 0.007 vs 0.072_amp_#xb1 0.01 P _amp_#x3c 0.01 |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-treated | 1.9 | Inflammation in the MOG-treated mice was associated with myelin loss as indicated by LFB |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-treated | 1.9 | Axonal staining of spinal cord sections from MOG-treated mice showed severe axonal damage using Bielshowesky_amp_#x2019 s method ( |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-treated | 1.9 | we found marked axonal loss in the spinal cords of MOG-treated mice compared to naive mice (0.44_amp_#xb1;0.03 0.44_amp_#xb1 0.03 vs 0.65_amp_#xb1 |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-treated | 1.9 | the riluzole-treated mice axonal integrity was preserved compared to the MOG-treated group (0.54_amp_#xb1;0.02 0.54_amp_#xb1 0.02 vs 0.44_amp_#xb1 0.03 P _amp_#x3c 0.02 |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-treated | 1.9 | Based on such testing the spinal cords of MOG-treated mice showed an increase of abnormal dephosphorylated NF-H ( Fig |
| 7737 | NEFH | neurofilament, heavy polypeptide 200kDa | NF-H | 0.3 | cords of MOG-treated mice showed an increase of abnormal dephosphorylated NF-H ( Fig 2G while minimal abnormal dephosphorylation was observed in |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-treated | 1.9 | Pro Plus analysis we found massive axonal damage in the MOG-treated mice compared to naive mice (0.03_amp_#xb1;0.003 0.03_amp_#xb1 0.003 vs 0.0005_amp_#xb1 |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-treated | 1.9 | in the area stained by SMI-32 as compared to the MOG-treated group (0.0006_amp_#xb1;0.0001 0.0006_amp_#xb1 0.0001 vs 0.03_amp_#xb1 0.003 P _amp_#x3c 0.0001 |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-treated | 1.9 | We compared the T-cell response in the riluzole- and MOG-treated mice groups to rule out the possibility that the observed |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-treated | 1.9 | Riluzole-treated and MOG-treated mice (three three in each group were immunized with pMOG |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG | 1.9 | Fig 4 the in vitro primary proliferative response of both MOG and riluzole-treated mice against pMOG 35_amp_#x2013 55 was similar |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-induced | 1.9 | study shows that riluzole-treated C3H.SW mice are highly resistant to MOG-induced chronic EAE |
| 7737 | NEFH | neurofilament, heavy polypeptide 200kDa | NF-H | 0.3 | demonstrated axonal disruption indicating a large increase of abnormally dephosphorylated NF-H in MOG-immunized spinal cords in the riluzole-treated mice there was |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-immunized | 1.9 | disruption indicating a large increase of abnormally dephosphorylated NF-H in MOG-immunized spinal cords in the riluzole-treated mice there was minimal abnormal |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | MOG-immunized | 1.9 | for pMOG 35_amp_#x2013 55 was similar in the riluzole-treated and MOG-immunized mice suggesting that the beneficial effect of riluzole is probably |
| 4573 | GRIA3 | glutamate receptor, ionotrophic, AMPA 3 | GluR3 | 1.6 | found high expression of the glutamate ion channel receptor (GluR3) GluR3 on normal human T-cells human T leukemia cells and mouse |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | myelin oligodendrocyte glycoprotein | 1.0 | encephalomyelitis eae the conventional model of ms. therefore we examined whether riluzole an inhibitor of glutamate transmission affects the pathogenesis and clinical features of ms like disease in myelin oligodendrocyte glycoprotein mog induced eae in mice. |
| 4571 | GRIA1 | glutamate receptor, ionotropic, AMPA 1 | glutamate receptor | 1.0 | recent studies suggest that glutamate neurotoxicity is involved in the pathogenesis of multiple sclerosis ms and that treatment with glutamate receptor ampa/kainate antagonists inhibits experimental autoimmune encephalomyelitis eae the conventional model of ms. therefore we examined whether riluzole an inhibitor of glutamate transmission affects the |
| 7197 | MOG | myelin oligodendrocyte glycoprotein | myelin oligodendrocyte glycoprotein | 1.0 | we therefore investigated the clinical effects of riluzole in reducing the insult to neurons and axons in myelin oligodendrocyte glycoprotein mog induced eae in c3h.sw mice a chronic model which appears to resemble the clinical course of progressive ms better than the other disorders induced by auto antigens [ 27 ]. |
| 4571 | GRIA1 | glutamate receptor, ionotropic, AMPA 1 | glutamate receptor | 1.0 | glutamate receptor mediated toxicity has been observed in an oligodendroglial cell line [ 28 ] and in cultures of differentiated oligodendrocytes [ 26 and 42 ] and in an animal model for ms [ 44 ]. |
| 4341 | GLUL | glutamate-ammonia ligase (glutamine synthetase) | glutamine synthetase | 1.0 | hardin et al. [ 21 ] showed that expression of glutamine synthetase and glutamate dehydrogenase the enzymes that are responsible for glutamate degradation was dramatically reduced in astrocytes during the course of eae affecting the reuptake of glutamate. |
| 4571 | GRIA1 | glutamate receptor, ionotropic, AMPA 1 | glutamate receptor | 1.0 | however based on several previous studies showing that the csf glutamate levels are increased in ms patients [ 2 ] and that glutamate receptor antagonists ameliorate neurological symptoms in several forms of eae [ 38 and 43 ] it is tempting to suggest that it works by the suppression of glutamatergic neurotransmission in the cns achieved by |
| 6925 | MBP | myelin basic protein | myelin basic protein | 1.0 | a recent study found high expression of the glutamate ion channel receptor glur3 on normal human t cells human t leukemia cells and mouse anti myelin basic protein t cells [ 18 ]. |
| 6783 | MAG | myelin associated glycoprotein | myelin associated glycoprotein | 1.0 | myelin associated glycoprotein|neuroprotective agents|oligodendrocyte myelin glycoprotein|riluzole| |