My research interests over the years have included studies of membrane biochemistry, myelination, myelin metabolism, and the mechanism of myelin breakdown in demyelinating diseases (e.g., MS). Research goals have been directed to identification of factor(s) which may be responsible for myelin breakdown in MS and other neurodegenerative diseases. Subsequent studies on myelin dissolution in vitro and in vivo models, including CNS injury, delineated a role for proteolytic enzyme(s) in tissue destruction. We have identified and implicated a major proteolytic enzyme -- calpain, a calcium activated neutral proteinase -- to play an initial role in tissue breakdown in health and disease, particularly in spinal cord injury and demyelinating diseases. These studies are continuing in experimental animal models. I have localized calpain in myelin by biochemical and immunocytochemical methods and examined how it may be regulated. I am currently studying the source of this enzyme in CNS injury and demyelinating diseases and have taken cellular and molecular approaches to study its expression both at the gene and protein levels. Findings of its increased activity and content in CNS trauma led me to examine whether: 1) calpain stimulation and expression is regulated by cytokines (or other factors); and, 2) use of calpain-specific inhibitors as therapeutic agents in spinal cord injury and in close animal models of MS will be neuroprotective.