The Structural and Biochemical Organization of Myelin in Health and Pathology

This review examines current understanding of myelin biology and its adaptive roles in health, disease, and aging. We describe the cell populations involved in myelination, demyelination, and remyelination. We discuss the microstructural organization of myelin and its maintenance through complex molecular interactions within the glial microenvironment. We summarize morphological changes in myelin associated with various neurological disorders of the central and peripheral nervous systems. We note the fundamental biochemical differences between central nervous system (CNS) and peripheral nervous system (PNS) myelin and describe potential mechanisms underlying pathological molecular alterations. This review discusses recent and sometimes conflicting evidence on adaptive and maladaptive myelin plasticity, the role of myelin function in aging, the relationship between myelin and the microbiota, and the involvement of myelin in gray matter neurodegeneration. We present relevant data on myelin vulnerability and myelin degradation as potential markers of neurodegeneration in animal models. This review summarizes current understanding of the key cellular and molecular mediators of physiological myelination and pathological demyelination and examines the molecular mechanisms underlying these processes.