Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by irreversible deterioration of upper and lower motor neurons (MNs). Previously, studies on the involvement of glial cells in the pathogenic process of ALS have mainly revolved around astrocytes and microglia. And oligodendrocytes (OLs) have only recently been highlighted. Grey matter demyelination within the motor cortex and proliferation of the oligodendrocyte precursor cells (OPCs) was observed in ALS patients. The selective ablation of mutant SOD1 (the dysfunctional superoxide dismutase) from the oligodendrocyte progenitors after birth significantly delayed disease onset and prolonged the overall survival in ALS mice model (SOD1 G37R). In this study, we review the several mechanisms of oligodendrocyte dysfunction involved in the pathological process of myelin damage and MNs death during ALS. Particularly, we examined the insufficient local energy supply from OLs to axons, impaired differentiation from OPCs into OLs mediated by oxidative stress damage, and inflammatory injury to the OLs. Since increasing evidence depicted that ALS is not a disease limited to MNs damage, exploring the mechanisms by which oligodendrocyte dysfunction is involved in MNs death would contribute to a more comprehensive understanding of ALS and identifying potential drug targets.
Keywords: amyotrophic lateral sclerosis; energy metabolism; neuroinflammation; oligodendrocytes; oxidative stress.