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.
© 2011 Mount Sinai School of Medicine.
Publication types
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Research Support, American Recovery and Reinvestment Act
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Activities of Daily Living
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Adult
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Animals
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Aspartic Acid / analogs & derivatives
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Aspartic Acid / metabolism
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Axons* / metabolism
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Axons* / pathology
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Humans
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Immunity / drug effects
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Immunologic Factors* / metabolism
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Immunologic Factors* / therapeutic use
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Inflammation / immunology
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Inflammation / physiopathology
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Multiple Sclerosis* / metabolism
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Multiple Sclerosis* / pathology
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Multiple Sclerosis* / physiopathology
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Multiple Sclerosis* / therapy
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Myelin Sheath* / metabolism
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Myelin Sheath* / pathology
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Nerve Degeneration* / metabolism
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Nerve Degeneration* / pathology
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Nervous System Autoimmune Disease, Experimental / metabolism
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Nervous System Autoimmune Disease, Experimental / pathology
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Nervous System Autoimmune Disease, Experimental / physiopathology
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Nervous System Autoimmune Disease, Experimental / therapy
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Positron-Emission Tomography
Substances
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Immunologic Factors
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Aspartic Acid
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N-acetylaspartate