Final Report Summary - AXOGLIA (Understanding the axon-glial functional unit in myelination and remyelination) Myelination of nerve fibres by glial cells, oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS), gives rise to the axon/glia functional unit with its unique properties, e.g. axon protection, and increased resistance and decreased capacitance across large calibre axons for fast saltatory conduction of action potentials. The importance of the myelination process is highlighted by the fact that loss or damage of myelin is one of the major mechanisms underlying the pathology of devastating neurological disorders including leukodystrophies, central and peripheral neuropathies, and inflammatory demyelinating diseases such as multiple sclerosis (MS). These diseases present a high incidence, severe symptoms and a poor treatment outcome. Thus, they represent a serious health as well as economic and social burden at European level (Gustavsson et al., 2011). Remyelination, the process by which demyelinated axons are reinvested with new myelin sheath following demyelination, is required to ensure recovery of physiological activity of the nerves (Bruce et al., 2007). Spontaneous remyelination in human demyelinating diseases can occur, but it is an uneven process often insufficient to preserve axon integrity and, ultimately, proper physiological activity. It is possible that during demyelination and remyelination expression of key signaling molecules is altered. Long-term axon protection could therefore be achieved only through the re-establishment of an efficient axon/myelin functional unit cross-talk. According to this hypothesis, only a “correct” remyelination consisting in the preservation of the original axonal and myelin expressed proteome could potentially reduce axonal loss. Over the past few years it has been realized that the interaction of myelinating glia with axons is bidirectional and recent data suggest that the myelinating glia plays an active role in the maintenance of axon integrity, whose preservation could be the key to prevent chronic progressive disability (Edgar and Garbern, 2004; Lubetzki et al., 2005; Zawadzka and Franklin, 2007). Despite the importance of these processes, no clear understanding of the key molecules and signalling pathways involved and altered in demyelination and remyelination is presently available (Bruce et al., 2007). Our lack of a clear understanding of the general mechanisms underlying myelination and remyelination arises in part from the fact that most of the studies have been relying on conventional molecular, biochemical and cellular methodologies which permit to successfully address one or a few identified molecules of interest but cannot provide a complete profile of the complex events underlying these processes.This fellowship aimed to combine this classical approach to systems biology approach. Conventional molecular, biochemical and cellular methodologies have been applied to study a previously identified interesting candidate (i.e. Profilin 1, see 1 below) for its role in PNS and CNS myelination. A system biology approach has been applied to identify new potential candidates likely to play a role in CNS myelination/remyelination (or its failure) (see 2 below). Related documents Microsoft Word - Summary_final_report.doc
