Nrf2 Pathway in Huntington's Disease (HD): What Is Its Role?

Abstract

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that occurs worldwide. Despite some progress in understanding the onset of HD, drugs that block or delay symptoms are still not available. In recent years, many treatments have been proposed; among them, nuclear transcriptional factor-2 (Nrf2) enhancer compounds have been proposed as potential therapeutic agents to treat HD. Nrf2 triggers an endogenous antioxidant pathway activated in different neurodegenerative disorders. Probably, the stimulation of Nrf2 during either the early phase or before HD symptoms' onset, could slow or prevent striatum degeneration. In this review, we present the scientific literature supporting the role of Nrf2 in HD and the potential prophylactic and therapeutic role of this compound.

Keywords: Huntington’s disease; Nrf2; antioxidant; neurodegenerative disease; oxidative stress.

Figure 1

The consequence of the toxic protein mHTT synthesis in the HD (created in BioRender.com).

Figure 2

Keap1–Nrf2 Pathway. The oxidative stress leading to Nrf2 nuclear translocation and antixiodant transcription (created in BioRender.com). ? indicates no demonstrated mechanism in neurodegenerative disorders.

Figure 3

Evidence from substances treatment supporting a role for Nrf2 in HD. This figure reports a summary of results from substances tested in vitro and/or in vivo. The yellow rectangles reported substances active on the Nrf2 pathway in the different models (created in BioRender.com).