title: Axonal damage in multiple sclerosis.
abstract: Multiple sclerosis is a debilitating disease of the central nervous system that has been characteristically classified as an immune-mediated destruction of myelin, the protective coating on nerve fibers. Although the mechanisms responsible for the immune attack to central nervous system myelin have been the subject of intense investigation, more recent studies have focused on the neurodegenerative component, which is cause of clinical disability in young adults and appears to be only partially controlled by immunomodulatory therapies. Here, we review distinct, but not mutually exclusive, mechanisms of pathogenesis of axonal damage in multiple sclerosis patients that are either consequent to long-term demyelination or independent from it. We propose that the complexity of axonal degeneration and the heterogeneity of the underlying pathogenetic mechanisms should be taken into consideration for the design of targeted therapeutic intervention.
authors.affiliation: Departments of Neuroscience Neurology and Genetics and Genomics, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Haines
authors.forename: Matilde
authors.initials: M
authors.lastname: Inglese
authors.forename: Patrizia
authors.initials: P
authors.lastname: Casaccia
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007109:Immunity / Q000187:drug effects; D007155:Immunologic Factors / Q000378:metabolism / Q000627:therapeutic use; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D020721:Nervous System Autoimmune Disease, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D049268:Positron-Emission Tomography
chemical_list: D007155:Immunologic Factors; D001224:Aspartic Acid; C000179:N-acetylaspartate