Understanding the intricacies of cellular mechanisms in remyelination: The role of circadian rhythm

Abstract

The term “circadian rhythm” refers to the 24-h oscillations found in various physiological processes in organisms, responsible for maintaining bodily homeostasis. Many neurological diseases mainly involve the process of demyelination, and remyelination is crucial for the treatment of neurological diseases. Current research mainly focuses on the key role of circadian clocks in the pathophysiological mechanisms of multiple sclerosis. Various studies have shown that the circadian rhythm regulates various cellular molecular mechanisms and signaling pathways involved in remyelination. The process of remyelination is primarily mediated by oligodendrocyte precursor cells (OPCs), oligodendrocytes, microglia, and astrocytes. OPCs are activated, proliferate, migrate, and ultimately differentiate into oligodendrocytes after demyelination, involving many key signaling pathway and regulatory factors. Activated microglia secretes important cytokines and chemokines, promoting OPC proliferation and differentiation, and phagocytoses myelin debris that inhibits remyelination. Astrocytes play a crucial role in supporting remyelination by secreting signals that promote remyelination or facilitate the phagocytosis of myelin debris by microglia. Additionally, cell-to-cell communication via gap junctions allows for intimate contact between astrocytes and oligodendrocytes, providing metabolic support for oligodendrocytes. Therefore, gaining a deeper understanding of the mechanisms and molecular pathways of the circadian rhythm at various stages of remyelination can help elucidate the fundamental characteristics of remyelination and provide insights into treating demyelinating disorders.