Epidermal Growth Factor Pathway in the Age-Related Decline of Oligodendrocyte Regeneration

Abstract

Oligodendrocytes (OLs) are specialized glial cells that myelinate CNS axons. OLs are generated throughout life from oligodendrocyte progenitor cells (OPCs) via a series of tightly controlled differentiation steps. Life-long myelination is essential for learning and to replace myelin lost in age-related pathologies such as Alzheimer’s disease (AD) as well as white matter pathologies such as multiple sclerosis (MS). Notably, there is considerable myelin loss in the aging brain, which is accelerated in AD and underpins the failure of remyelination in secondary progressive MS. An important factor in age-related myelin loss is a marked decrease in the regenerative capacity of OPCs. In this review, we will contextualize recent advances in the key role of Epidermal Growth Factor (EGF) signaling in regulating multiple biological pathways in oligodendroglia that are dysregulated in aging.