The Myelin Membrane of the Central Nervous System—Essential Macromolecular Structure and Function

The neural sheaths that surround the nerve fibers (axons) are composed of myelin-specific complex lipids and are assembled during the myelination phase either by the oligodendrocytes in the central nervous system (CNS) or by the Schwann cells in the peripheral nervous system. These multilayered myelin membranes insulate the axons and permit a rapid, saltatory conduction of excitation and a reduced axon diameter in comparison with noninsulated axons. Myelination was hence the decisive evolutionary event in miniaturization of the central nervous system (brain and spinal cord). The morphology of the myelin membrane has been studied in detail mainly by electron microscopy. Most of its biochemistry has been elucidated in recent years by molecular-level analysis of both the lipid components (cholesterol, phospholipids and sphingolipids) and the constituent proteins. The multilamellar system is distinguished by a characteristic periodicity due to the 5-nm-thick bilayer formed by the myelin-specific lipids. The bilayer interacts with the myelin basic protein (MBP) on the cytosolic side of the plasma membrane process, while the integral membrane protein proteolipid protein (PLP) has hydrophilic domains exposed on both the cytosolic and extracytosolic faces of the bilayer. Numerous protein-chemical and -immunotopochemical findings have been summarized in a model of the myelin membrane. Through molecular biological studies, the genetic structure and chromosomal location of the myelin proteins have been determined. By employing techniques of molecular and cell biology together, it is now possible to analyze the process of myelinogenesis, the time- and location-specific expression of myelin-specific genes in the brain. Gene-technological methods have been used to define the mutations in the models jimpy mouse and myelin-deficient rat. These are animal models that correspond to genetically determined myelin defects (dysmyelinoses) in humans. Using them, it will be possible to study the cell death of oligodendrocytes on a molecular level; this process is the result of expression of mutant myelin proteins and is incompatible with life. Oligodendrocytes and the myelin structures they synthesize are the target structures of cytotoxic lymphocytes (T_c). In the course of the demyelination process in multiple sclerosis, these cause the breakdown of the myelin sheaths, in gradually appearing inflammations. T_c lymphocytes recognize myelin structures as epitopes and destroy them. The picture of the myelin membrane's molecular composition, which we are now perfecting, will also lead to a better understanding of demyelination on a molecular level, and hence to new therapeutic possibilities.