title: Oxidative stress mediates tau-induced neurodegeneration in Drosophila.
abstract: Markers of oxidative damage have been detected in brain tissue from patients with Alzheimer disease (AD) and other neurodegenerative disorders. These findings implicate oxidative injury in the neurodegenerative process, but whether oxidative stress is a cause or a consequence of neurotoxicity remains unclear. We used a Drosophila model of human tauopathies to investigate the role of oxidative stress in neurodegeneration. Genetic and pharmacological manipulation of antioxidant defense mechanisms significantly modified neurodegeneration in our model, suggesting that oxidative stress plays a causal role in neurotoxicity. We demonstrate that the JNK signaling pathway is activated in our model, which is in agreement with previous findings in AD tissue. Furthermore, we show that the extent of JNK activation correlates with the degree of tau-induced neurodegeneration. Finally, our findings suggest that oxidative stress acts not to promote tau phosphorylation, but to enhance tau-induced cell cycle activation. In summary, our study identifies oxidative stress as a causal factor in tau-induced neurodegeneration in Drosophila.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Dora
authors.initials: D
authors.lastname: Dias-Santagata
authors.forename: Tudor A
authors.initials: TA
authors.lastname: Fulga
authors.forename: Atanu
authors.initials: A
authors.lastname: Duttaroy
authors.forename: Mel B
authors.initials: MB
authors.lastname: Feany
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D004330:Drosophila; D006801:Humans; D009410:Nerve Degeneration / Q000473:pathology* / Q000517:prevention & control; D018384:Oxidative Stress / Q000502:physiology*; D010269:Paraquat / Q000633:toxicity; D024801:Tauopathies / Q000473:pathology* / Q000503:physiopathology; D014810:Vitamin E / Q000494:pharmacology*; D016875:tau Proteins / Q000633:toxicity*
chemical_list: D016875:tau Proteins; D014810:Vitamin E; D010269:Paraquat