Mechanism of demyelination and remyelination in multiple sclerosis

Abstract

AbstractRecent insights into its molecular neuropathology and immunology have provided a comprehensive overview of the pathology of multiple sclerosis (MS), including demyelination and axonal loss. To date, neuropathology in MS as the human autoimmune disease is considered to be mainly mediated by autoreactive leukocytes. By contrast, accumulating evidence has also suggested that the inflammation and tissue damage in MS and its animal model, experimental autoimmune encephalomyelitis, (EAE) is also critically regulated by glial cells in the central nervous system. However, the molecular mechanism of the glial cells‐mediated pathology of MS/EAE has not been fully understood. We examined the oligodendrocyte‐mediated demyelination and axonal injury. To address this issue, we established a new scanning electron microscopy analysis to observe ultrastructural myelin morphology. In addition, we focused on kallikrein 6, a serine protease, secreted by oligodendrocytes in the central nervous system and proposed a new molecular mechanism of kallikrein 6‐mediated demyelination. In this article, we discuss the pathological roles of oligodendrocytes in mouse models of EAE. We also highlight recent findings of abnormal myelin formation and axonal injury in EAE.