An overview of the molecular mechanisms and novel roles of Nrf2 in neurodegenerative disorders

Cytokine Growth Factor Rev. 2015 Feb;26(1):47-57. doi: 10.1016/j.cytogfr.2014.09.002. Epub 2014 Sep 16.

Abstract

Recently, growing evidence has demonstrated that nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal regulator of endogenous defense systems that function via the activation of a set of protective genes, and this is particularly clear in the central nervous system (CNS). Therefore, it is highly useful to summarize the current literature on the molecular mechanisms and role of Nrf2 in the CNS. In this review, we first briefly introduce the molecular features of Nrf2. We then discuss the regulation, cerebral actions, upstream modulators and downstream targets of Nrf2 pathway. Following this background, we expand our discussion to the role of Nrf2 in several major neurodegenerative disorders (NDDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis. Lastly, we discuss some potential future directions. The information reviewed here may be significant in the design of further experimental research and increase the potential of Nrf2 as a therapeutic target in the future.

Keywords: Cerebrum actions; Molecular mechanisms; Neurodegenerative disorders; Nuclear factor erythroid 2-related factor 2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Animals
  • Brain / physiology
  • Humans
  • Huntington Disease / genetics
  • Huntington Disease / physiopathology
  • Mice
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / physiopathology
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / physiopathology*
  • Parkinson Disease / genetics
  • Parkinson Disease / physiopathology
  • Signal Transduction*

Substances

  • NF-E2-Related Factor 2