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AMP-activated Protein Kinase Signaling Activation by Resveratrol Modulates Amyloid-β Peptide Metabolism

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Vingtdeux, Valérie, Giliberto, Luca, Zhao, Haitian, Chandakkar, Pallavi, Wu, Qingli, Simon, James E., Janle, Elsa M., Lobo, Jessica, Ferruzzi, Mario G., Davies, Peter, Marambaud, Philippe·2010·Journal of Biological Chemistry
DOI 10.1074/jbc.m109.060061
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Abstract

Alzheimer disease is an age-related neurodegenerative disorder characterized by amyloid-beta (Abeta) peptide deposition into cerebral amyloid plaques. The natural polyphenol resveratrol promotes anti-aging pathways via the activation of several metabolic sensors, including the AMP-activated protein kinase (AMPK). Resveratrol also lowers Abeta levels in cell lines; however, the underlying mechanism responsible for this effect is largely unknown. Moreover, the bioavailability of resveratrol in the brain remains uncertain. Here we show that AMPK signaling controls Abeta metabolism and mediates the anti-amyloidogenic effect of resveratrol in non-neuronal and neuronal cells, including in mouse primary neurons. Resveratrol increased cytosolic calcium levels and promoted AMPK activation by the calcium/calmodulin-dependent protein kinase kinase-beta. Direct pharmacological and genetic activation of AMPK lowered extracellular Abeta accumulation, whereas AMPK inhibition reduced the effect of resveratrol on Abeta levels. Furthermore, resveratrol inhibited the AMPK target mTOR (mammalian target of rapamycin) to trigger autophagy and lysosomal degradation of Abeta. Finally, orally administered resveratrol in mice was detected in the brain where it activated AMPK and reduced cerebral Abeta levels and deposition in the cortex. These data suggest that resveratrol and pharmacological activation of AMPK have therapeutic potential against Alzheimer disease.

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Metadata

Authors
Vingtdeux, V., Giliberto, L., Zhao, H., Chandakkar, P., Wu, Q., Simon, J. E., Janle, E. M., Lobo, J., Ferruzzi, M. G., Davies, P., & Marambaud, P.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2010-03
Volume
285
Issue
12
Pages
9100-9113
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m109.060061
OpenAlex
W2068383276
Cited by
645
References
15
FWCI
26.63
Type
journal article
Language
en
Open access
hybrid
Licence

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CoChat. (2026). Citation check: AMP-activated Protein Kinase Signaling Activation by Resveratrol Modulates Amyloid-β Peptide Metabolism. https://app.cochat.ai/papers/10.1074/jbc.m109.060061
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Vingtdeux, V., Giliberto, L., Zhao, H., Chandakkar, P., Wu, Q., Simon, J. E., Janle, E. M., Lobo, J., Ferruzzi, M. G., Davies, P., & Marambaud, P. (2010). AMP-activated Protein Kinase Signaling Activation by Resveratrol Modulates Amyloid-β Peptide Metabolism. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m109.060061

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