title: The modest impact of transcription factor Nrf2 on the course of disease in an ALS animal model.
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.
authors.affiliation: Department of Neurology, the Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Yansu
authors.initials: Y
authors.lastname: Guo
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Wen
authors.forename: Weisong
authors.initials: W
authors.lastname: Duan
authors.forename: Ting
authors.initials: T
authors.lastname: An
authors.forename: Pengxiao
authors.initials: P
authors.lastname: Shi
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.forename: Zhongyao
authors.initials: Z
authors.lastname: Li
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chen
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
mesh_terms: D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000502:physiology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D055786:Gene Knockout Techniques; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation
chemical_list: D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D005721:Glutamate-Cysteine Ligase