Nrf2: a modulator of Parkinson’s disease?

Parkinson’s disease (PD) is a complex multifactorial disorder that has been associated with the processes of oxidative stress. In the absence of curative therapies, modification of the neurodegenerative process—including the manipulation of endogenous antioxidant pathways—is the focus of intensive research. Recently, genetic and pharmacological accretion of the transcription factor, and phase II antioxidant ‘master regulator’ Nrf2, has shown to demonstrably mitigate the toxic neuronal effects of parkinsonian agents such as MPP⁺, rotenone, and hydrogen peroxide in vitro and in vivo. Furthermore, baseline genetic variability in Nrf2-dependant pathways may promote neuronal susceptibility to exogenous agents and correlate with PD onset within certain populations. While contemporary evidence directly implicating Nrf2 in the pathogenesis of PD is not conclusive and likely contingent upon the evaluation of complex interacting factors—including genetic variation and a history of environmental exposures—it remains a promising target for therapeutic benefit in the modulation of oxidative stress.