Sirtuin 3 Mediates Tau Deacetylation

Department

neurology

Document Type

Article

Abstract

Background: Emerging evidence shows tau acetylation has been observed in Alzheimer's disease (AD) brain at early Braak stages and is involved in regulating tau early accumulation. However, the effects of deacetylase Sirtuin 3 (Sirt3) on tau acetylation and its aggregations are unclear. Objective: We studied the effects of Sirt3 on tau acetylation and its aggregations. Methods: We investigated the protein levels of Sirt3 and tangle tau in human postmortem brains slices from AD, mild cognitive impairment, and age- and education-matched cognitively normal subjects, and AD model mice. We also measured tau acetylation levels in hippocampal HT22 cells after Sirt3 knockdown or overexpression. Results: The level of Sirt3 was inversely related with tau protein in brain slices from both human being and AD model mice. Mechanistically, tau acetylation decreased dramatically with Sirt3 overexpression, while tau acetylation increased after Sirt3 knockdown in hippocampal HT22 cells. Conclusions: Sirt3 may play a role in tau acetylation and could be a potential target for novel therapy to alleviate tau accumulation.

Medical Subject Headings

neurology

Publication Date

2019

Publication Title

Journal of Alzheimer's Disease

ISSN

1387-2877

Volume

69

Issue

2

First Page

355

Last Page

362

Digital Object Identifier (DOI)

10.3233/JAD-190014

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