Oxidative stress and impaired oligodendrocyte precursor cell differentiation in neurological disorders

Jan Spaas, Lieve van Veggel, Melissa Schepers, Assia Tiane, Jack van Horssen, David M. Wilson, Pablo R. Moya, Elisabeth Piccart, Niels Hellings, Bert O. Eijnde, Wim Derave, Rudy Schreiber, Tim Vanmierlo*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

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 inflammation-induced demyelination (remyelination) but are also pivotal in plastic processes such as learning and memory (adaptive myelination). OPC differentiation 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 differentiation, 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 affect 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 differentiation remain enigmatic and a focus of current research efforts. This review proposes a role for oxidative/carbonyl stress in interfering with the transcriptional and metabolic changes required for OPC differentiation. In particular, oligodendrocyte (epi)genetics, cellular defence and repair responses, mitochondrial signalling and respiration, and lipid metabolism represent key mechanisms how oxidative/carbonyl stress may hamper OPC differentiation in neurodegenerative disorders. Understanding how oxidative/carbonyl stress impacts OPC function may pave the way for future OPC-targeted treatment strategies in neurodegenerative disorders.
Original languageEnglish
Pages (from-to)4615-4637
Number of pages23
JournalCellular and Molecular Life Sciences
Volume78
Issue number10
Early online date2021
DOIs
Publication statusPublished - May 2021

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