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Oxidative stress mediates tau-induced neurodegeneration in Drosophila
Open accessAbstract
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.
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“Pan-neuronal transgenic expression of an FTDP-17 mutant form of human tau, tauR406W, in Drosophila causes progressive neurodegeneration and provides a well-characterized in vivo genetic model of tau neurotoxicity7,15,16.”
From Tau promotes neurodegeneration through global chromatin relaxation (2014) · cites this paper as [16]
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“No statistical methods were used to predetermine sample sizes but our sample sizes are similar to those reported in previous publications 7,16,44.”
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“In addition, neuronal phenotypes of tau transgenic Drosophila mimic features of human Alzheimer’s disease and associated tauopathies, including but not limited to aberrant tau phosphorylation13, oxidative stress14, DNA damage15,16, decondensation of constitutive heterochromatin10, synaptic dysfunction17 and activation of the cell cycle in post-mitotic neurons18.”
From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [14]
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Metadata
- Authors
- Dias-Santagata, D., Fulga, T. A., Duttaroy, A., & Feany, M. B.
- Affiliations
- Brigham and Women's Hospital (US)
- Howard University (US)
- Venue
- Journal of Clinical Investigation
- Published
- 2007-01-02
- Volume
- 117
- Issue
- 1
- Pages
- 236-245
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1697799
- OpenAlex
- W1997198091
- Cited by
- 318
- References
- 61
- Citations by year
- 2026: 6 · 2025: 22 · 2024: 20 · 2023: 21 · 2022: 21 · 2021: 24 · 2020: 15 · 2019: 16 · 2018: 14 · 2017: 15 · 2016: 15 · 2015: 21 · 2014: 14 · 2013: 7 · 2012: 13
- FWCI
- 7.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brigham and Women's Hospital
- National Institutes of Health (AG005134)
- Fundação para a Ciência e a Tecnologia (SFRH/BPD/20685/2004)
- National Institute on Aging (AG005134, AG-19790, P50AG005134, R01AG019790)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- oxidative stress, tau protein, tauopathy, neurodegeneration, Alzheimer's disease, JNK signaling, antioxidant defense, cell cycle activation, Drosophila model, tau phosphorylation
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Drosophila, Humans, Nerve Degeneration, Paraquat, Vitamin E, tau Proteins, Oxidative Stress, Tauopathies
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