The Nrf2/ARE pathway as a potential therapeutic target in neurodegenerative disease.
Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to induce expression of a variety of cytoprotective and detoxification genes. Several of the genes commonly regulated by Nrf2 have been implicated in protection from neurodegenerative conditions. Work from several laboratories has uncovered the potential for Nrf2-mediated transcription to protect from neurodegeneration resulting from mechanisms involving oxidative stress. For this reason, Nrf2 may be considered a therapeutic target for conditions that are known to involve free radical damage. Because common mechanisms of neurodegeneration, such as mitochondrial dysfunction and build-up of reactive oxygen species, are currently being uncovered, targeting Nrf2 may be valuable in combating conditions with variable causes and etiologies. Most effectively to target this protein in neurodegenerative conditions, a description of the involvement of Nrf2 and potential for neuroprotection must come from laboratory models. Herein, we review the current literature that suggests that Nrf2 may be a valuable therapeutic target for neurodegenerative disease, as well as experiments that illustrate potential mechanisms of protection.
Calkins
Marcus J
MJ
Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin 53705, USA.
Johnson
Delinda A
DA
Townsend
Jessica A
JA
Vargas
Marcelo R
MR
Dowell
James A
JA
Williamson
Tracy P
TP
Kraft
Andrew D
AD
Lee
Jong-Min
JM
Li
Jiang
J
Johnson
Jeffrey A
JA
D006801:Humans; D008962:Models, Theoretical; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism*
D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human