The projects contained in this proposal are all closely related to the central theme of interactions of motor nerves and skeletal muscles. Myasthenia gravis (MG) is by far the most common clinical disorder of the neuromuscular junction, affecting acetylcholine receptors. We will continue our analysis of the pathogenetic mechanisms in MG, and will undertake therapeutic trials in experimental animals. We will extend our studies of neurotrophic mechanisms, both at the level of the nerve's influence, and at the level of the muscle's response. We will study nerve sprouting and regeneration, with particular emphasis on the factors that evoke nerve growth and the axonal mechanisms by which it is sustained. We have begun an extensive study of Coxsackievirus myopathy. This viral myopathy relates closely to the theme of the proposal, because only denervated or immature muscles are susceptible to infection, and because surface receptors are essential for infection to take place. Thus, the virus will be used as a biological probe of the muscle membrane during development and denervation. Finally, we plan to continue our studies of axonal transport in normal and abnormal peripheral nerve regeneration.
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