AMPK Ameliorates Tau Acetylation and Memory Impairment Through Sirt1
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AMPK Ameliorates Tau Acetylation and Memory Impairment Through Sirt1 Lin Wang 1,2 & Fang-Xiao Shi 1 & Na Li 1 & Yun Cao 1 & Ying Lei 1 & Jian-Zhi Wang 1 & Qing Tian 1 & Xin-Wen Zhou 1 Received: 5 June 2020 / Accepted: 14 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disease, but its underlying mechanism is still unclear and the identities of drugs for AD also lack. Tau acetylation has become potentially important post-translational modification of tau. Levels of tau acetylation are significantly enhanced in AD patients and transgenic mouse models of AD, but the underlying mechanism and roles of tau hyperacetylation in AD onset maintain elusive. In the current study, we found that tau acetylation is obviously enhanced and the activities of AMP-activated protein kinase (AMPK) and sirtuin1 (Sirt1) are significantly decreased in APP/PS1 and streptozotocin (STZ) mice and high glucose (HG)-treated cells. Moreover, we demonstrated that activation of AMPK reduces the level of tau acetylation and ameliorates memory impairment, and its mechanism is associated with activation of Sirt1. Taken together, AMPK might be a crucial upstream molecular to regulate acetylation of tau and become a new target for AD therapy in the future. Keywords Alzheimer’s disease . AMPK . Tau acetylation . Sirt1
Introduction Alzheimer’s disease (AD) currently afflicts more than 35 million people worldwide [1], and the Delphi study predicted that this number will rise to 81.1 million in 2040 [2]. AD is an agerelated neurodegenerative disease characterized pathologically by the presence of amyloid-β (Aβ) peptides in extracellular senile plaques and the formation of intracellular neurofibrillary tangles (NFTs) composed of aberrantly phosphorylated tau(p-tau) [3, 4]. Tau undergoes a number of post-translational modifications, such as phosphorylation [5], acetylation [6, 7], ubiquitination [8], methylation [9], and sumoylation [10], Lin Wang and Fang-Xiao Shi contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02079-x) contains supplementary material, which is available to authorized users. * Xin-Wen Zhou [email protected] 1
Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry Education of China and Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2
Department of Pathophysiology, Wannan Medical College, Wuhu 241001, China
which can modulate the function, turnover, or multimeric assembly of tau protein. Mounting evidence has demonstrated that abnormally modified tau is associated with AD pathogenesis. Phosphorylation is the most well-studied post-translational modification of tau by far, its phosphorylation sites have been described at least 40, and up to 25 of these may undergo increa
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