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Resveratrol Promotes Clearance of Alzheimer's Disease Amyloid-β Peptides
Open accessAbstract
Several epidemiological studies indicate that moderate consumption of wine is associated with a lower incidence of Alzheimer's disease. Wine is enriched in antioxidant compounds with potential neuroprotective activities. However, the exact molecular mechanisms involved in the beneficial effects of wine intake on the neurodegenerative process in Alzheimer's disease brain remain to be clearly defined. Here we show that resveratrol (trans-3,4',5-trihydroxystilbene), a naturally occurring polyphenol mainly found in grapes and red wine, markedly lowers the levels of secreted and intracellular amyloid-beta (Abeta) peptides produced from different cell lines. Resveratrol does not inhibit Abeta production, because it has no effect on the Abeta-producing enzymes beta- and gamma-secretases, but promotes instead intracellular degradation of Abeta via a mechanism that involves the proteasome. Indeed, the resveratrol-induced decrease of Abeta could be prevented by several selective proteasome inhibitors and by siRNA-directed silencing of the proteasome subunit beta5. These findings demonstrate a proteasome-dependent anti-amyloidogenic activity of resveratrol and suggest that this natural compound has a therapeutic potential in Alzheimer's disease.
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Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., Zipkin, R. E., Chung, P., Kisielewski, A., Zhang, L.-L., et al. (2003) · Nature · doi:10.1038/nature01960 · Cited by 3,796
Lindsay, J. (2002) · American Journal of Epidemiology · doi:10.1093/aje/kwf074 · Cited by 1,261
Increased Nuclear NAD Biosynthesis and SIRT1 Activation Prevent Axonal Degeneration
Araki, T., Sasaki, Y., & Milbrandt, J. (2004) · Science · doi:10.1126/science.1098014 · Cited by 1,060
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Quideau, S., Deffieux, D., Douat‐Casassus, C., & Pouységu, L. (2011) · Angewandte Chemie International Edition · doi:10.1002/anie.201000044 · Cited by 2,730
Kim, D., Nguyen, M. D., Dobbin, M. M., Fischer, A., Sananbenesi, F., Rodgers, J. T., Delalle, I., Baur, J. A., Sui, G., Armour, S. M., et al. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601758 · Cited by 1,074
Autophagy and apoptosis dysfunction in neurodegenerative disorders
Ghavami, S., Shojaei, S., Yeganeh, B., Ande, S. R., Jangamreddy, J. R., Mehrpour, M., Christoffersson, J., Chaabane, W., Moghadam, A. R., Kashani, H. H., et al. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.10.004 · Cited by 1,039
Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future
Zhang, Y., Chen, H., Li, R., Sterling, K., & Song, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01484-7 · Cited by 988
Role of Phenolic Compounds in Human Disease: Current Knowledge and Future Prospects
Rahman, M. M., Rahaman, M. S., Islam, M. R., Rahman, F., Mithi, F. M., Alqahtani, T., Almikhlafi, M. A., Alghamdi, S. Q., Alruwaili, A. S., Hossain, M. S., et al. (2021) · Molecules · doi:10.3390/molecules27010233 · Cited by 852
Metadata
- Authors
- Marambaud, P., Zhao, H., & Davies, P.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 280
- Issue
- 45
- Pages
- 37377-37382
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2070815033
- Cited by
- 749
- References
- 4
- FWCI
- 15.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Marambaud, P., Zhao, H., & Davies, P. (2005). Resveratrol Promotes Clearance of Alzheimer's Disease Amyloid-β Peptides. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m508246200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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