Sirtuin 3 Mediates Tau Deacetylation

Article type: Research Article

Authors: Li, Shiping^{a; b; 1} | Yin, Junxiang^{b; 1} | Nielsen, Megan^{b; c} | Beach, Thomas G.^d | Guo, Li^{a; *} | Shi, Jiong^{b; e; f; *}

Affiliations: [a] Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China | [b] Barrow Neurological Institute, St. Joseph Hospital and Medical Center, Dignity Health Organization, Phoenix, AZ, USA | [c] College of Science, University of Arizona, Tucson, AZ, USA | [d] Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA | [e] Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China | [f] China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Correspondence: [*] Correspondence to: Li Guo, Department of Neurology, The Second Hospital of Hebei Medical University, No.215 Hepingxilu, Xinhua District, Shijiazhuang, 050000, Hebei, China. E-mail: [email protected] and Jiong Shi, MD, PhD, Advanced Innovation Center for Human Brain Protection, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, China and Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Dignity Health Organization, 240 W. Thomas Road, Phoenix, AZ 85013, USA. Tel.: +1 602 406 4032; Fax: +1 602 798 0899; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

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.

Keywords: Acetylation, Alzheimer’s disease, Sirtuin, tau

DOI: 10.3233/JAD-190014

Journal: Journal of Alzheimer's Disease, vol. 69, no. 2, pp. 355-362, 2019