Oxidative stress and impaired oligodendrocyte precursor cell differentiation in neurological disorders

Oligodendrocyte precursor cells (OPCs) account for 5% of the resident parenchymal central nervous system glial cells. OPCs are not only a back-up for the loss of oligodendrocytes that occurs due to brain injury or infammation-induced demyelination (remyelination) but are also pivotal in plastic processes such as learning and memory (adaptive myelination). OPC diferentiation into mature myelinating oligodendrocytes is controlled by a complex transcriptional network and depends on high metabolic and mitochondrial demand. Mounting evidence shows that OPC dysfunction, culminating in the lack of OPC diferentiation, mediates the progression of neurodegenerative disorders such as multiple sclerosis, Alzheimer’s disease and Parkinson’s disease. Importantly, neurodegeneration is characterised by oxidative and carbonyl stress, which may primarily afect OPC plasticity due to the high metabolic demand and a limited antioxidant capacity associated with this cell type.The underlying mechanisms of how oxidative/carbonyl stress disrupt OPC diferentiation remain enigmatic and a focus of current research eforts. This review proposes a role for oxidative/carbonyl stress in interfering with the transcriptional and metabolic changes required for OPC diferentiation. In particular, oligodendrocyte (epi)genetics