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Logo for the Journal of Rehab R&D
Volume 43 Number 1, January/February 2006
Pages 123 — 132


Abstract - Oligodendrocyte cell death in pathogenesis of multiple sclerosis: Protection of oligodendrocytes from apoptosis by complement

Cornelia Cudrici, MD;1 Teodora Niculescu, MD;1 Florin Niculescu, MD, PhD;2 Moon L. Shin, MD;3 Horea Rus, MD, PhD1,4*

Departments of 1Neurology, 2Medicine-Division of Rheumatology and Clinical Immunology, and 3Pathology, University of Maryland School of Medicine, Baltimore, MD; 4Department of Veterans Affairs (VA) Maryland Health Care System, Multiple Sclerosis Center of Excellence East, Baltimore VA Medical Center, Baltimore, MD
Abstract — Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. It is mediated by activated lymphocytes, macrophages, microglia, and complement. In MS, myelin-forming oligodendrocytes (OLGs) are the targets of inflammatory and immune attacks. OLG death by apoptosis or necrosis causes the cell loss seen in MS plaques. Studies of experimental allergic encephalomyelitis (EAE) in caspase 11-deficient mice show that caspase-mediated death of OLGs is critical to demyelination. Complement activation may affect MS pathogenesis through activated terminal complex C5b-9, which promotes demyelination, and through sublytic C5b-9, which protects OLGs from apoptosis. By inducing EAE in C5-deficient mice, we showed that complement C5 promotes axon preservation and new myelin formation, which protect OLGs from apoptosis. These findings indicate that activated complement C5b-9 plays a proinflammatory role in acute MS but may also protect OLGs from death in chronic MS.
Key words: apoptosis, caspases, complement C5, complement complex C5b-9, experimental allergic encephalomyelitis, Fas ligand, oligodendrocyte, multiple sclerosis, phosphatidylinositol-3 kinase, T lymphocyte.

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