The role of Nrf2 in neural stem/progenitors cells: From maintaining stemness and self-renewal to promoting differentiation capability and facilitating therapeutic application in neurodegenerative disease

Abstract

Neurodegenerative diseases (NDs) cause progressive loss of neurons in nervous system. NDs are categorized as acute NDs such as stroke and head injury, besides chronic NDs including Alzheimer's, Parkinson's, Huntington's diseases, Friedreich's Ataxia, Multiple Sclerosis. The exact etiology of NDs is not understood but oxidative stress, inflammation and synaptic dysfunction are main hallmarks. Oxidative stress leads to free radical attack on neural cells which contributes to protein misfolding, glia cell activation, mitochondrial dysfunction, impairment of DNA repair system and subsequently cellular death. Neural stem cells (NSCs) support adult neurogenesis in nervous system during injuries which is limited to certain regions in brain. NSCs can differentiate into the neurons, astrocytes or oligodendrocytes. Impaired neurogenesis and inadequate induction of neurogenesis are the main obstacles in treatment of NDs. Protection of neural cells from oxidative damages and supporting neurogenesis are promising strategies to treat NDs. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcriptional master regulator that maintains the redox homeostasis in cells by provoking expression of antioxidant, anti-inflammatory and cytoprotective genes. Nrf2 can strongly influence the NSCs function and fate determination by reducing levels of reactive oxygen species in benefit of NSC survival and neurogenesis. In this review we will summarize the role of Nrf2 in NSC function, and exogenous and endogenous therapeutic strategies in treatment of NDs.

Keywords: Nrf2 signaling; Oxidative/inflammatory stress; ROS metabolism; Stroke-induced secondary neurodegeneration.