The modest impact of transcription factor Nrf2 on the course of disease in an ALS animal model.

TitleThe modest impact of transcription factor Nrf2 on the course of disease in an ALS animal model.
Publication TypeJournal Article
Year of Publication2013
AuthorsGuo Y, Zhang Y, Wen D, Duan W, An T, Shi P, Wang J, Li Z, Chen X, Li C
JournalLaboratory investigation; a journal of technical methods and pathology
Volume93
Issue7
Pagination825-33
Date Published2013 Jul
Abstract

Oxidative stress is associated with the pathogenesis of amyotrophic lateral sclerosis (ALS). Nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is one of the major cellular defense mechanisms against oxidative stress. However, the role of Nrf2-mediated neuroprotection (antioxidant defense) in the disease development of ALS remains unclear. To further investigate the role of Nrf2 in ALS, we genetically eliminate the Nrf2 gene from SOD1-G93A mice, a commonly used ALS mouse model, by generating a double mutant (Nrf2-/- SOD1-G93A mice). We found that it only had a modest impact on the course of disease by knocking out Nrf2 gene in these mice. Further studies demonstrated that, among previously known Nrf2-regulated phase II enzymes, only NAD(P)H: quinone oxidoreductase 1 induction was significantly affected by the elimination of Nrf2 gene in SOD1-G93A mice. Taken together, our data suggested that Nrf2 is not the sole mediator for the induction of antioxidant genes in SOD1-G93A mice, and Nrf2-mediated neuroprotection is not the key protective mechanism against neurodegeneration in those mice.

DOI10.1039/c3an00948c
Alternate JournalLab. Invest.