SIRT1 facilitates amyloid beta peptide degradation by upregulating lysosome number in primary astrocytes

Neural Regeneration Research
Min-Zhe LiJian-Guo Ji

Abstract

Previous studies have shown that sirtuin 1 (SIRT1) reduces the production of neuronal amyloid beta (Aβ) and inhibits the inflammatory response of glial cells, thereby generating a neuroprotective effect against Aβ neurotoxicity in animal models of Alzheimer's disease. However, the protective effect of SIRT1 on astrocytes is still under investigation. This study established a time point model for the clearance of Aβ in primary astrocytes. Results showed that 12 hours of culture was sufficient for endocytosis of oligomeric Aβ, and 36 hours sufficient for effective degradation. Immunofluorescence demonstrated that Aβ degradation in primary astrocytes relies on lysosome function. Enzymatic agonists or SIRT1 inhibitors were used to stimulate cells over a concentration gradient. Aβ was co-cultured for 36 hours in medium. Western blot assay results under different conditions revealed that SIRT1 relies on its deacetylase activity to promote intracellular Aβ degradation. The experiment further screened SIRT1 using quantitative proteomics to investigate downstream, differentially expressed proteins in the Aβ degradation pathway and selected the ones related to enzyme activity of SIRT1. Most of the differentially expressed proteins detect...Continue Reading

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Citations

Apr 26, 2019·Journal of Cellular Biochemistry·Ziv Radisavljevic
Aug 30, 2019·Fluids and Barriers of the CNS·Louise DelsingJane Synnergren
Jan 11, 2020·Frontiers in Pharmacology·Mohammad Afaque Alam, Prasun K Datta
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Jan 2, 2021·Frontiers in Human Neuroscience·Sidra TabassumLi Yang
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Jul 3, 2021·Frontiers in Aging Neuroscience·Sanghamitra Bandyopadhyay
Dec 8, 2020·ACS Chemical Neuroscience·Keng Yoon YeongYuin Chang

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Methods Mentioned

BETA
transfection
electrophoresis
PCR
acetylation

Software Mentioned

Proteome Discoverer
Graphpad Prism
ImageJ
GENECODIS

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