Effects of mutant TDP-43 on the Nrf2/ARE pathway and protein expression of MafK and JDP2 in NSC-34 cells

Genetics and Molecular Research : GMR
Y P TianJ X Yu

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons and lacks an effective treatment. The disease pathogenesis has not been clarified at present. Pathological transactive response DNA-binding protein 43 (TDP-43) plays an important role in the pathogenesis of ALS. Nuclear translocation of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is found in a mutant TDP-43 transgenic cell model, but its downstream antioxidant enzyme expression is decreased. To elucidate the specific mechanism of Nrf2/ARE (antioxidant responsive element) signaling dysfunction, we constructed an ALS cell model with human mutant TDP-43 using the NSC-34 cell line to evaluate the impact of the TDP-43 mutation on the Nrf2/ARE pathway. We found the nuclear translocation of Nrf2, but the expression of total Nrf2, cytoplasmic Nrf2, and downstream phase II detoxifying enzyme (NQO1) was decreased in NSC-34 cells transfected with the TDP-43-M337V plasmid. Besides, TDP-43-M337V plasmid-transfected NSC-34 cells were rounded with reduced neurites, shortened axons, increased levels of intracellular lipid peroxidation products, and decreased viability, which suggests that the TDP-43-M337V plasmid weakened the antioxidan...Continue Reading

Citations

Jan 13, 2018·The FEBS Journal·Albena T Dinkova-KostovaAleksey G Kazantsev
Mar 7, 2019·Frontiers in Molecular Neuroscience·Archana PrasadBasant K Patel
Aug 5, 2019·Clinica Chimica Acta; International Journal of Clinical Chemistry·Carmen Peña-BautistaConsuelo Cháfer-Pericás
Dec 5, 2020·Oxidative Medicine and Cellular Longevity·Teresa Cunha-OliveiraFilomena S G Silva
Jul 28, 2021·Free Radical Biology & Medicine·J Jiménez-VillegasA I Rojo

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