Neurogenesis and neuroprotection in the CNS--fundamental elements in the effect of Glatiramer acetate on treatment of autoimmune neurological disorders.
Multiple sclerosis (MS) is no longer considered to be simply an autoimmune disease. 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 aim to act within the central nervous system (CNS) by interfering with both neuroinflammation and neurodegeneration. Specific treatment strategies to autoimmune neurological disorders should aim to act within the CNS by interfering with both neuroinflammation and neurodegeneration. The cumulative effect of Glatiramer acetate (GA; Copaxone(R), Copolymer 1), an approved drug for the treatment of MS, reviewed herewith, draws a direct linkage between anti-inflammatory immunomodulation, neuroprotection, neurogenesis, and therapeutic activity in the CNS. GA treatment augmented the three processes characteristic of neurogenesis, namely, neuronal progenitor cell proliferation, migration, and differentiation. The newborn neurons manifested massive migration through exciting and dormant migratory pathways, into injury sites in brain regions, which do not normally undergo neurogenesis, and differentiated to mature neuronal phenotype, thus, counteracting the neurodegenerative course of disease. 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.
Arnon
Ruth
R
The Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel. ruth.arnon@weizmann.ac.il
Aharoni
Rina
R
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy*; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation; D009410:Nerve Degeneration / Q000276:immunology / Q000503:physiopathology; D009422:Nervous System Diseases / Q000188:drug therapy / Q000276:immunology*; D010455:Peptides / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate