Loss or damage of myelin is one of the major mechanisms underlying the pathology of several neurological disorders, e.g. leukodystrophies, central and peripheral neuropathies, and inflammatory demyelinating diseases such as multiple sclerosis (MS), a serious health as well as economic and social burden at European level. Remyelination, the process by which demyelinated axons are reinvested with new myelin sheath, is required to ensure recovery of physiological activity of the nerves. Even if spontaneous remyelination in human demyelinating diseases can occur, it is an uneven process often insufficient to preserve axon integrity. Long-term axon protection could be achieved through the re-establishment of an efficient axon/myelin functional unit. Only a “correct” remyelination consisting in the preservation of the original axonal and myelin expressed proteome could potentially reduce axonal loss. No clear understanding of the key molecules involved in myelination and remyelination is at the moment available. Conventional molecular and cell biological assays do not provide a complete profile of the molecular changes involved in the establishment and maintenance of the myelin sheath. The fellow will apply a multidisciplinary approach. Forefront proteomics techniques (iTRAQ) will allow to profile the membrane proteins present at the axon/myelin interface and involved in initiating and maintaining myelination. The fellow will also address how remyelination, in a demyelinating animal model, differs from developmental myelination. The localization and specific function of a subset of interesting candidates will be analyzed in vitro and in vivo, in order to broaden our knowledge of the basic molecular processes underlying myelination/remyelination and to identify potential therapeutical targets. The fellowship will help Europe to become more prominent in the area of Systems biology, in which North America is at the moment leading, and strengthen European collaborations.
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