Oligodendrocytes in health and disease

The cell biological mechanisms that govern myelin sheath extension remain incompletely understood. Here, the authors find that calcium signaling in oligodendrocytes is required for the actin-dependent extension of myelin sheaths.

Heterozygous deletions in the ANKS1B gene cause ANKS1B neurodevelopmental syndrome. Here the authors show this syndrome is associated with impaired white matter integrity, and that Anks1b-deficient mouse models display deficits in oligodendrocyte maturation, myelination, and Rac1 function.

How oligodendrocyte precursor cells (OPCs) integrate calcium signals and neuromodulatory cues to regulate fate is unclear. Here, the authors report that locomotion-induced norepinephrine release modulates OPC calcium dynamics and differentiation.

Niemann-Pick type C disease is characterized by deficiency of the endolysosomal cholesterol transporter NPC1. Here, the authors show in Npc1^−/− mice that loss of NPC1 impairs oligodendrocyte lineage cell differentiation and developmental myelination through perturbed epigenetic regulation.

The mechanisms regulating central nervous system remyelination efficiency are poorly understood. Here, the authors show that remyelination is driven by astrocytes supporting oligodendrocyte survival, regulated by the Nrf2 and cholesterol pathways.

Oligodendrocytes have been increasingly shown to be involved in Alzheimer’s disease (AD). Here, the authors perform single-cell RNA-sequencing on APP NL-G-F mice and describe a disease-associated oligodendrocyte (DAO) population. They find inhibition of Erk1/2 signaling in DAOs rescues impaired axonal myelination and cognitive decline in an AD mouse model.