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- W1963554273 abstract "A hallmark of Alzheimer's disease (AD) is the accumulation of plaques of Abeta 1-40 and 1-42 peptides, which result from the sequential cleavage of APP by the beta and gamma-secretases. The production of Abeta peptides is avoided by alternate cleavage of APP by the alpha and gamma-secretases. Here we show that production of beta-amyloid and plaques in a mouse model of AD are reduced by overexpressing the NAD-dependent deacetylase SIRT1 in brain, and are increased by knocking out SIRT1 in brain. SIRT1 directly activates the transcription of the gene encoding the alpha-secretase, ADAM10. SIRT1 deacetylates and coactivates the retinoic acid receptor beta, a known regulator of ADAM10 transcription. ADAM10 activation by SIRT1 also induces the Notch pathway, which is known to repair neuronal damage in the brain. Our findings indicate SIRT1 activation is a viable strategy to combat AD and perhaps other neurodegenerative diseases." @default.
- W1963554273 created "2016-06-24" @default.
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- W1963554273 date "2010-07-01" @default.
- W1963554273 modified "2023-09-30" @default.
- W1963554273 title "RETRACTED: SIRT1 Suppresses β-Amyloid Production by Activating the α-Secretase Gene ADAM10" @default.
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- W1963554273 doi "https://doi.org/10.1016/j.cell.2010.06.020" @default.
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