Neuroprotection by central nervous system remyelination: Molecular, cellular, and functional considerations

Oligodendrocytes and their myelin sheaths play an intricate role in axonal health and function. The prevalence of white matter pathology in a wide variety of central nervous system disorders has gained attention in recent years. Remyelination has therefore become a major target of therapeutic research, with the aim of protecting axons from further damage. The axon-myelin unit is elaborate, and demyelination causes profound changes in axonal molecular domains, signal transmission, and metabolism. Remyelination is known to restore some of these changes, but many of its outcomes remain unknown. Understanding how different aspects of the axon-myelin unit are restored by remyelination is important for making effective, targeted therapeutics for white matter dysfunction. Additionally, understanding how subtle deficits relate to axonal function during demyelination and remyelination may provide clues into the impact of myelin on neuronal circuits. In this review, we discuss the current knowledge of the neuroprotective effects of remyelination, as well as gaps in our knowledge. Finally, we propose systems with unique myelin profiles that may serve as useful models for investigating remyelination efficacy. © 2016 Wiley Periodicals, Inc.