Nrf2 as a Potential Therapeutic Target for Treatment of Huntington’s Disease

Abstract

Oxidative stress-induced neuronal damage plays a significant role in pathogenesis of several neuro-degenerative disorders including Huntington’s disease. In Huntington’s disease, oxidative stress-induced neuronal damage is reported to be mediated by PGC-1α and microglial cells. This development led to various clinical trials that tested the efficacy of several exogenous antioxidants such as vitamin E, vitamin C, etc. to prevent the oxidative stress-induced cell damage in several neuro-degenerative disorders. But these randomized clinical trials did not find any significant beneficial effects of exogenous antioxidants in neuro-degenerative disorders. This forced scientists to search endogenous targets that would enhance the production of antioxidants. Nrf2 is one such ideal target that increases the transcription of genes involved in production of antioxidants. Nrf2 is a transcription factor that controls the expression of antioxidant genes that defend cells against oxidative stress. This chapter focuses on the role of oxidative stress in Huntington’s disease and explores the therapeutic benefits of Nrf2 activators.