Oxidative stress and impaired oligodendrocyte precursor cell differentiation in neurological disorders

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.

Demyelination of the Optic Nerve: An Underlying Factor in Glaucoma?

“…Oxidative stress and mitochondrial damage can promote each other, forming a vicious cycle ( Mahad et al, 2015 ). According to a previous study, oxygen free radicals can attack DNA in oligodendrocytes, and oxidative stress can also affect mitochondrial membrane phospholipids, enzymes, protein complexes, and mtDNA ( Spaas et al, 2021 ). Oxidative stress attacks other components, in addition to mitochondrial damage.…”

Cofilin and Neurodegeneration: New Functions for an Old but Gold Protein

“…During the development of the central nervous system, oligodendrocyte precursor cells are responsible for extending a network of processes to contact axons and initiate myelination [ 52 ]. In this action, the dynamics of the cytoskeleton is vital, and any alteration in both the formation and repair of myelin generates neurodegenerative diseases such as AD, multiple sclerosis, amyotrophic lateral sclerosis, or psychiatric diseases [ 53 , 54 , 55 ].…”

Mitochondria in Early Forebrain Development: From Neurulation to Mid-Corticogenesis

“…This question is compelling especially since the movement and structure of mitochondria in oligodendrocytes and myelin sheaths are specialized ( Rinholm et al, 2016 ) and modulate their Ca 2+ levels ( Ruiz et al, 2020 ) and oligodendrocytes are a key source of lactate to neurons ( Rinholm et al, 2016 ). From a developmental angle, metabolic perturbations can disrupt oligodendrocyte maturation ( Spaas et al, 2021 ). Finally, microglia, the CNS-specific tissue-resident macrophages depend on mitochondrial energy metabolism states for their M1/M2 polarization between pro-inflammatory vs. resolution/repair function, with ramifications for CNS development, maintenance, and response to injury and repair ( Orihuela et al, 2016 ).…”