"Peripheral nerve myelination by Schwann cells is essential for normal nervous system function. Numerous acquired and inherited diseases result from defects in peripheral nerve myelination or myelin maintenance. In addition myelination is crucial for repair and regeneration of the nervous system. Thus an important challenge is to understand the cellular and molecular events that underlie myelination and myelin maintenance. The host laboratory, under the direction of Dr Nicolas Tricaud, has developed a novel in vivo approach to investigate the basic molecular mechanisms that control myelination, myelin maintenance and demyelination. This technique involves microinjection of viral vectors that express cDNAs and small inhibitory RNAs in myelinating Schwann cells of mice. The aim of the present proposal is to use this approach to analyse the basic cellular mechanisms, with particular focus on cell-cell interactions, involved in the aetiology of demyelinating peripheral neuropathies. In addition increasing evidence suggests that numerous hereditary and acquired peripheral nerves diseases present with significant mitochondrial dysfunctions. The relationship between the function of mitochondria in mSCs and in peripheral axons remains unknown. Therefore the second aim of this project is to investigate both the role of mitochondria in mSCs and to evaluate the impact of glial mitochondrial activities on the physiology and function of the myelinated axon. The present proposal will provide key information about peripheral myelination and maintenance with particular relevance to the aetiology of peripheral neuropathies, information crucial for the development of therapeutic strategies for these highly debilitating diseases."
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