Neuroprotection and neurogeneration in MS and its animal model EAE effected by glatiramer acetate.
It is by now established that multiple sclerosis (MS) is not simply an autoimmune disease and that in addition to inflammation and demyelination, axonal injury and neuronal loss underlie the accumulation of disability and the disease progression. Specific treatment strategies should thus target the injury sites at the central nervous system (CNS) to interfere with both neuroinflammation and neurodegeneration. Glatiramer acetate (GA Copaxone, Copolymer 1), an approved drug for the treatment of multiple sclerosis, was shown earlier to act as an anti-inflammatory and immunomodulatory agent. In this mini-review its effect on neuroprotection, neurogenesis and on the remyelination process is delineated in the EAE model. The plausible mechanism underlying this multifactorial effect is the induction of GA-reactive T-cells in the periphery and their infiltration into the CNS, where they release immunomodulatory cytokines and neurotrophic factors in the injury site, suggesting a direct linkage to its therapeutic effect in both EAE and MS.
Arnon
Ruth
R
The Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel. ruth.arnon@weizmann.ac.il
Aharoni
Rina
R
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use
D016207:Cytokines; D007166:Immunosuppressive Agents; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D010455:Peptides; D000068717:Glatiramer Acetate