title: Nrf2 inducer and cncC overexpression attenuates neurodegeneration due to α-synuclein in Drosophila.
abstract: The study of the genes that are related to the pathogenesis of Parkinson's disease (PD) will improve our understanding of the mechanisms that underlie the development of PD. α-Synuclein is a major protein component of Lewy bodies, which are characteristic structures of PD pathology. Mutations in α-synuclein are closely related to the early onset of autosomal dominant PD. Transgenic flies with mutant α-synuclein (A53T) display neurodegenerative changes that include movement dysfunctions and a loss of dopaminergic neurons in the brain. In the present study, we measured reactive oxygen species (ROS) levels in α-synuclein transgenic flies by monitoring the fluorescence levels of redox-sensitive indicators based on GFP (roGFP) in flies co-expressing roGFP and mutant α-synuclein. We found that the ROS levels were significantly increased in the mutant α-synuclein flies. The elevations in ROS levels were also proportionate to the behavioral disorders and the losses of dopaminergic neurons. We also found that CDDO-Me inhibited the increases in ROS levels in the A53T flies and improved the neurodegenerative changes by activating the Nrf2/antioxidant response element signaling pathway. Selective expression of the Nrf2 homologous gene cncC in the dopaminergic neurons effectively protected against the neurodegenerative phenotype of the A53T α-synuclein flies, compared to the flies that expressed cncC in all neurons. These results indicate that the reductions in oxidative stress that are mediated by the activation of the antioxidant signaling pathway can effectively attenuate the neurotoxicity caused by mutations in α-synuclein.
authors.affiliation: Department of Human Anatomy and Cytoneurobiology, Medical School of Soochow University, Suzhou, P. R. China.|Department of Human Anatomy and Cytoneurobiology, Medical School of Soochow University, Suzhou, P. R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Human Anatomy and Cytoneurobiology, Medical School of Soochow University, Suzhou, P. R. China.|Department of Human Anatomy and Cytoneurobiology, Medical School of Soochow University, Suzhou, P. R. China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Human Anatomy and Cytoneurobiology, Medical School of Soochow University, Suzhou, P. R. China.|Department of Human Anatomy and Cytoneurobiology, Medical School of Soochow University, Suzhou, P. R. China.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Shan
authors.affiliation: Department of Human Anatomy and Cytoneurobiology, Medical School of Soochow University, Suzhou, P. R. China.|Department of Human Anatomy and Cytoneurobiology, Medical School of Soochow University, Suzhou, P. R. China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Xia
authors.affiliation: Department of Human Anatomy and Cytoneurobiology, Medical School of Soochow University, Suzhou, P. R. China.|Department of Human Anatomy and Cytoneurobiology, Medical School of Soochow University, Suzhou, P. R. China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics*; D005260:Female; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D051267:NF-E2-Related Factor 2; D012097:Repressor Proteins; D051844:alpha-Synuclein; C116463:cnc protein, Drosophila
keywords: Nrf2; Parkinson’s disease; espèce réactive d’oxygène; maladie de Parkinson; reactive oxygen species; α-synuclein; α-synucléine