Disease-associated oligodendroglia: a putative nexus in neurodegeneration

Neural cells in our central nervous system (CNS) have long been thought to be mere targets of neuroinflammatory events in neurodegenerative diseases such as multiple sclerosis (MS) or Alzheimer's disease. While glial populations such as microglia and astrocytes emerged as active responders and modifiers of pathological environments, oligodendroglia and neurons have been associated with altered homeostasis and eventual cell death. The advent of single-cell and spatial omics technologies has demonstrated transitions of CNS-resident glia, including oligodendroglia, into disease-associated (DA) states. Anchored in recent findings of their roles in MS, we propose that DA glia constitute key nexus of disease progression, with DA oligodendroglia contributing to the modulation of neuroinflammation in certain neurodegenerative diseases, constituting novel putative pharmacological targets for such pathologies.