Central nervous system myelin: structure, function, and pathology

Abstract

Multiple sclerosis (MS) and a number of related distinctive diseases are characterized by the active degradation of central nervous system (CNS) myelin, an axonal sheath comprised essentially of proteins and lipids. These demyelinating diseases appear to arise from complex interactions of genetic, immunological, infective, and biochemical mechanisms. While circumstances of MS etiology remain hypothetical, one persistent theme involves recognition by the immune system of myelin-specific antigens derived from myelin basic protein (MBP), the most abundant extrinsic myelin membrane protein, and/or another equally susceptible myelin protein or lipid component. Knowledge of the biochemical and physical-chemical properties of myelin proteins and lipids, particularly their composition, organization, structure, and accessibility with respect to the compacted myelin multilayers, thus becomes central to the understanding of how and why these antigens become selected during the development of MS. This review focuses on current understanding of the molecular basis underlying demyelinating disease as it may relate to the impact of the various protein and lipid components on myelin morphology; the precise molecular architecture of this membrane as dictated by protein-lipid and lipid-lipid interactions; and the relationship, if any, between the protein/lipid components and the destruction of myelin in pathological situations.

Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS

“…CNS myelin is rich in nonproteic molecules (22) and shows little protein content (23). Moreover, the presence of antibodies against myelin lipids has been reported in other demyelinating diseases of the peripheral nervous system (24,25).…”

Three-dimensional Structure of Myelin Basic Protein

“…1 is one of the most important proteins of the myelin sheath (1)(2)(3)(4)(5)(6). Its significance is demonstrated in the shiverer mutant of mouse, which has only a small amount of structurally unstable myelin because the gene for MBP is mostly deleted (7,8).…”

Inflammatory response of the spinal cord to multiple episodes of blood-brain barrier disruption and toxic demyelination in Wistar rats

“…The findings suggest that no exposure of an antigenic myelin fragment that could induce an immune demyelinating response occurred in EB-induced lesions, although the antigenic potential of some myelin components, such as myelin basic protein, has been demonstrated (2,17).…”

“…Environmental and genetic factors could also be involved, as well as a viral agent (19), that may incite a cross-reaction against myelin basic protein (17) or actually cause the disease (17,18,20). Some investigators (20) suggest that the etiology of multiple sclerosis is multifactorial, and that sclerosis only occurs when some of these factors coincide in the same individual.…”

“…Thus, it is likely that many factors, besides blood-brain barrier disruption, are involved in immune-mediated demyelinating processes in the CNS, such as multiple sclerosis, including autoimmune factors (18) such as T helper (Th) lymphocytes specific against myelin basic protein and activation of astrocytes, endothelial cells or microglia (17). Environmental and genetic factors could also be involved, as well as a viral agent (19), that may incite a cross-reaction against myelin basic protein (17) or actually cause the disease (17,18,20).…”