Redox-regulated fate of neural stem progenitor cells

Background: Accumulated data indicate that self-renewal, multipotency, and differentiation of neural stem cells are under an intrinsic control mediated by alterations in the redox homeostasis. These dynamic redox changes not only reflect and support the ongoing metabolic and energetic processes, but also serve to coordinate redox-signaling cascades. Controlling particular redox couples seems to have a relevant impact on cell fate decision during development, adult neurogenesis and regeneration.

Scope of review: Our own research provided initial evidence for the importance of NAD+-dependent enzymes in neural stem cell fate decision. In this review, we summarize recent knowledge on the active role of reactive oxygen species, redox couples and redox-signaling mechanisms on plasticity and function of neural stem and progenitor cells focusing on NAD(P)+/NAD(P)H-mediated processes.

Major conclusions: The compartmentalized subcellular sources and availability of oxidizing/reducing molecules in particular microenvironment define the specificity of redox regulation in modulating the delicate balance between stemness and differentiation of neural progenitors. The generalization of "reactive oxygen species" as well as the ambiguity of their origin might explain the diametrically-opposed findings in the field of redox-dependent cell fate reflected by the literature.

General significance: Increasing knowledge of temporary and spatially defined redox regulation is of high relevance for the development of novel approaches in the field of cell-based regeneration of nervous tissue in various pathological states. This article is part of a special issue entitled Redox regulation of differentiation and de-differentiation.