Molecular pathogenesis of multiple sclerosis.
Multiple sclerosis (MS) is best understood as an inflammatory disease of the central nervous system (CNS) white matter characterized by demyelination, focal T cell and macrophage infiltrates, axonal injury and loss of neurological function. Our current understanding invokes proinflammatory cells and mediators that may be triggered by environmental factors to mediate disease in a genetically susceptible host. Five major themes which have been associated with the pathogenesis of MS lesions will be discussed: (1) The differential activation states of myelin-reactive T cells from MS patients vs. normal individuals, (2) the selective expression of chemokines, adhesion molecules and matrix metalloproteinases, (3) the proposed roles of the B7 costimulatory pathway, (4) the proinflammatory cytokines and (5) the role of molecular mimicry.
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Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115-5187, USA.
Oliveira
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Anderson
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Hafler
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D015551:Autoimmunity; D018122:B7-1 Antigen / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D008954:Models, Biological; D018716:Molecular Mimicry; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology; D009186:Myelin Sheath / Q000378:metabolism
D018122:B7-1 Antigen; D015815:Cell Adhesion Molecules; D018925:Chemokines; D020782:Matrix Metalloproteinases