Molecular Mechanisms of Oligodendrocyte Regeneration in White Matter-Related Diseases

Even in adult brains, restorative mechanisms are still retained to maintain the microenvironment. Under the pathological conditions of central nervous system (CNS) diseases, several immature cells in the brain would be activated as a compensative response. As the concept of the neurovascular unit emphasizes, cell-cell interactions play important roles in this restorative process. White matter damage and oligodendrocyte loss are representative characteristics for many neurodegenerative diseases. In response to oligodendrocyte damage, residual oligodendrocyte precursor cells (OPCs) initiate their proliferation and differentiation for the purpose of remyelination. Although mechanisms of oligodendrogenesis and remyelination in CNS diseases are still mostly unknown and understudied, accumulated evidence now suggests that support from neighboring cells is necessary for OPC proliferation and differentiation. In this review, we first overview basic mechanisms of interaction between oligodendrocyte lineage cells and neighboring cells, and then introduce how oligodendrogenesis occurs under the conditions of neurodegenerative diseases, focusing on vascular cognitive impairment syndrome, Alzheimer’s disease, and multiple sclerosis.