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Nat Rev Immunol. 2009 Jun;9(6):440-7. doi: 10.1038/nri2548.

A molecular trio in relapse and remission in multiple sclerosis.

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Department of Neurology and Neurological Sciences, Interdepartmental Program in Immunology, Beckman Center for Molecular Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.


Two thirds of patients with multiple sclerosis have the relapsing-remitting form, which often progresses to more debilitating disease. Striking clinical recovery, termed remission, often follows these periodic neurological defects, termed relapses. Recent work has revealed the role of three key molecules in relapse and remission: alpha4beta1 integrin (also known as VLA4) is an adhesion molecule that mediates T cell migration from the blood into the brain; osteopontin binds to alpha4beta1 integrin, stimulating the production of pro-inflammatory cytokines and inhibiting apoptosis; and alphaB crystallin inhibits inflammation in the brain. This Review discusses how this molecular trio interacts to initiate relapses (in the case of osteopontin and alpha4beta1 integrin) and then to terminate them as remissions in multiple sclerosis (in the case of alphaB crystallin).

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