Oligodendrocyte and Myelin Pathophysiology in Multiple Sclerosis.

Abstract

Multiple sclerosis (MS) is a chronic autoimmune and progressive neurodegenerative disease of the central nervous system (CNS) that has a highly variable clinical manifestation and course. MS targets primarily myelin and oligodendroglia; however, all glial cells and neurons become involved early in the pathology. Thus, inflammation, which is widely thought to be initiated peripherally, expands through the CNS, with astrocytes and microglia entering an activated state not only around and within lesions but also widespread. This chapter will emphasize the pathophysiological changes in oligodendrocytes and myelin as a consequence of the inflammatory cascade driving the disease onset and progression. Learning about the mechanisms of oligodendrocyte and myelin damage beyond the immune attack will be instrumental in protecting these two CNS compartments from damage. In turn, knowledge about the axon-myelin unit will help in devising therapies to prevent axonal degeneration, a key clinical hallmark of MS, as it strongly correlates with the progression of CNS atrophy and symptoms. Finally, exploiting paradigms of oligodendrocyte repopulation and remyelination will definitively contribute to devising treatments for tissue repair and halting MS course. This chapter aims at summarizing the state of the art in all these experimental developments including the available clinical therapies and the current clinical trials.