Oligodendrocytes in Huntington's Disease: A Review of Oligodendrocyte Pathology and Current Cell Reprogramming Approaches for Oligodendrocyte Modelling of Huntington's Disease.

Abstract

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder traditionally characterized by the selective loss of medium spiny neurons in the basal ganglia. However, it has become apparent that white matter injury and oligodendrocyte dysfunction precede the degeneration of medium spiny neurons, garnering interest as a key pathogenic mechanism of HD. Oligodendrocytes are glial cells found within the central nervous system involved in the production of myelin and the myelination of axons. Myelin is a lipid-rich sheath that wraps around axons, facilitating signal conduction and neuronal viability. The degeneration of myelin hinders effective communication and leaves neurons vulnerable to external damage and subsequent degeneration. Abnormalities in oligodendrocyte maturation have been established in the HD human brain, however, investigations into the underlying dysfunction of human oligodendrocytes in HD are limited. This review will detail the involvement of oligodendrocytes and white matter damage in HD. Recent developments in modeling human-specific oligodendrocyte pathology in HD will be discussed, with a particular focus on emerging somatic cell reprogramming approaches.