机构：[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重点科室诊疗科室神经病学中心神经病学中心首都医科大学附属天坛医院
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.
基金：
National Institute on AgingUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [P30 AG19610]; Arizona Department of Health Services [211002]; Barrow Neurological Foundation [3032226]; Flinn Foundation [2190]; National Science Foundation of ChinaNational Natural Science Foundation of China [81671050]
第一作者机构：[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
共同第一作者：
通讯作者：
通讯机构：[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[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[*1]Department of Neurology, The Second Hospital of Hebei Medical University, No.215 Hepingxilu, Xinhua District, Shijiazhuang, 050000, Hebei, China.[*2]Advanced Innovation Center for Human Brain Protection, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, China[*3]Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Dignity Health Organization, 240 W. Thomas Road, Phoenix, AZ 85013, USA.
推荐引用方式(GB/T 7714)：
Shiping Li,Junxiang Yin,Megan Nielsen,et al.Sirtuin 3 Mediates Tau Deacetylation[J].JOURNAL OF ALZHEIMERS DISEASE.2019,69(2):355-362.doi:10.3233/JAD-190014.
APA：
Shiping Li,Junxiang Yin,Megan Nielsen,Thomas G. Beach,Li Guo&Jiong Shi.(2019).Sirtuin 3 Mediates Tau Deacetylation.JOURNAL OF ALZHEIMERS DISEASE,69,(2)
MLA：
Shiping Li,et al."Sirtuin 3 Mediates Tau Deacetylation".JOURNAL OF ALZHEIMERS DISEASE 69..2(2019):355-362
