Biology of Demyelinating Diseases

Demyelinating diseases are those in which myelin is the primary target of damage on the basis of neuroradiological, neuropatholgical, neurochemical, and genetic studies. This review describes the morphological aspects of the myelin sheath which is the most abundant membrane structure in the vertebrate nervous system. It is made of oligodendrocytes in the CNS and Schwann cells in the PNS. It comprises four distinct regions: the node of Ranvier which contains voltage-gated Na+ channels, paranodal loops which are major sites of myelin-axon adhesion, the juxtaparanode, and the internode which is the part of the axon which is ensheathed by a segment of myelin. Demyelination is segmental in the peripheral nervous system and focal in the central nervous system. Myelin is necessary for nerve conduction velocity. Dys- and demyelination can involve specific constituents of the CNS and the PNS both for genetic (leukodystrophies) or acquired diseases. Numerous components are different and differently involved in CNS and PNS myelin, both among proteins and lipids (sphingolipids). Outside of the abnormalities of specific myelin components leading to genetic diseases, experimental models of demyelination (experimental autoimmune encephalomyelitis, cuprizone intoxication, lysolecithin-induced demyelination, and ethidium bromide treatment are also described). During myelin repair, a thinner myelin sheath is produced with shorter internodes and efficient nerve conduction is produced. Dysfunction of astrocytes may be involved in some genetic diseases of myelin. There are many growth factors and transcription factors involved in the process of myelination and demyelination among which eukaryotic initiation factor 2B (elf2B) leading to vanishing white matter disease (CACH). The role of hormones and sexual dimorphism of oligodendrocytes and myelin anre also described. New areas of research are being developed showing the involvement of myelin deficiency in psychiatric diseases and cognition.