Myelin biogenesis

Myelin membrane biogenesis and maintenance require a tight regulation of complex intracellular trafficking machineries, involving appropriate and sequential transportation of major myelin lipids and proteins to their final destination, where they can exert their function. As the function of major myelin lipids and proteins are closely related with their localisation, any alteration in the itinerary of biosynthesis and transportation of these molecules might dramatically change the biogenesis of these specialized membranes. For example, in demyelinating diseases such as MS, the localisation and organisation of myelin specific components are perturbed, leading to (de novo) myelin biogenesis failure, caused, among others, by an altered extracellular environment.

The work described in this thesis has provided new and detailed insight into mechanisms that regulate the trafficking, localisation and lateral organisation of the major myelin proteins PLP and MBP in response to intrinsic elements, such as the myelin typical galactolipids galactosylceramide and sulfatide, and extrinsic elements, such as physiological and disease-associated extracellular matrix proteins and pro-inflammatory cytokines. The obtained knowledge improves our understanding why biogenesis or maintenance of myelin fails in MS, thereby contributing to the elucidation of potential repair mechanisms, which is crucial for the development of an effective therapeutic approach in MS.