This program project deals with myelination, demyelination, and remyelination as it pertains to multiple sclerosis (MS). Project 1 is concerned with immunocyte function (particularly that of T suppressor cells and monocytes) in MS and how it can be manipulated so as to favorably influence the course of the disease. Suppressor function is decreased when MS is active, whereas monocyte function is increased. Emphasis is placed on beta2-adrenergic and muscarinic cholinergic receptors on lymphocytes and monocytes and their role in cell function. Both classes of receptor are up-regulated on immunocytes in progressive MS. Project 2 deals with proteoglycans and glycoproteins synthesized by oligodendrocyte known as OMgp which has been cloned and sequenced. The function of OMgp remains to be determined and is a major goal of Project 3. There is reason to believe, based on its structure, that OMgp will prove to be an adhesion molecule. Project 4 is directed towards Theiler's virus-induced demyelination as a model for the demyelination that characterized MS. The goal is to establish the determinants on Theiler's virus responsible for demyelination using molecular biologic techniques. The entire genome of three strains of Theiler's virus has been sequenced which should facilitate this task. Project 6 is directed to a study of the effects of cytokines on ion channels in sympathetic neurons. There are extensive interactions between the various projects and the two cores - Core A administrative and Core B scientific. The latter provides patient and control samples to the various projects.
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