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The modest impact of transcription factor Nrf2 on the course of disease in an ALS animal model.
|Title||The modest impact of transcription factor Nrf2 on the course of disease in an ALS animal model.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Guo Y, Zhang Y, Wen D, Duan W, An T, Shi P, Wang J, Li Z, Chen X, Li C|
|Journal||Laboratory investigation; a journal of technical methods and pathology|
|Date Published||2013 Jul|
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.
|Alternate Journal||Lab. Invest.|