Pathophysiological role of calpain in experimental demyelination

Calcium-activated neutral proteinase (calpain) has been extensively studied over the past three decades such that many enzymatic and structural properties of this enzyme are well understood. However, the pathophysiological roles of calpain remain poorly defined. In addition to recent studies delineating a role for calpain in various pathological conditions, this proteinase has been implicated in the degradation of myelin proteins in autoimmune demyelinating diseases such as multiple sclerosis and experimental allergic encephalomyelitis (EAE). In EAE, calpain translational expression is significantly increased in activated glial/inflammatory cells that participate in myelinolysis while calpain substrates (axonal and myelin proteins) are lost. Thus, since all major myelin proteins are calpain substrates, early studies suggest calpain may play an important role in demyelination of the central nervous system.