Hyperphosphorylation Results in Tau Dysfunction in DNA Folding and Protection

	Hyperphosphorylation Results in Tau Dysfunction in DNA Folding and Protection
	Lu, Yang 1,2; He, Hai-Jin 1; Zhou, Jun 1,4; Miao, Jun-Ye 1,4; Lu, Jing 1; He, Ying-Ge 1; Pan, Rong 1; Wei, Yan 1; Liu, Ying1 ; He, Rong-Qiao 1,3; He, RQ (reprint author), Chinese Acad Sci, State Key Lab Brain & Cognit Sci, Inst Biophys, 15 Datun Rd, Beijing 100101, Peoples R China.
心理所单位排序	1,3
摘要	Hyperphosphorylation of tau occurs in preclinical and clinical stages of Alzheimer's disease (AD), and hyperphosphorylated tau is the main constituent of the paired helical filaments in the brains of mild cognitive impairment and AD patients. While most of the work described so far focused on the relationship between hyperphosphorylation of tau and microtubule disassembly as well as axonal transport impairments, both phenomena ultimately leading to cell death, little work has been done to study the correlation between tau hyperphosphorylation and DNA damage. As we showed in this study, tau hyperphosphorylation and DNA damage co-occurred under formaldehyde treatment in N2a cells, indicating that phosphorylated tau (p-Tau) induced by formaldehyde may be involved in DNA impairment. After phosphorylation, the effect of tau in preventing DNA from thermal denaturation was diminished, its ability to accelerate DNA renaturation was lost, and its function in protecting DNA from reactive oxygen species (ROS) attack was impaired. Thus, p-Tau is not only associated with the disassembly of the microtubule system, but also plays a crucial role in DNA impairment. Hyperphosphorylation-mediated dysfunction of tau protein in prevention of DNA structure from damage under the attack of ROS may provide novel insights into the mechanisms underlying tauopathies.
关键词	Alzheimer's disease DNA protection formaldehyde GSK-3 beta phosphorylation tau hyperphosphorylation tau protein tauopathy
学科领域	Physiological Psychology/biological Psychology
	2013
语种	英语
发表期刊	JOURNAL OF ALZHEIMERS DISEASE
ISSN	1387-2877
卷号	37 期号:3 页码:551-563
期刊论文类型	期刊论文
URL	查看原文
收录类别	SCI
项目简介	We thank Dr. Chan-Shuai Han for helpful comments in the experimental design and the entire He group for critical discussion of the manuscript. We also appreciate Dr. Goedert and Dr. Torsten Juelich for kindly providing the Prk172 vector and language editing, respectively. This project was supported by the 973-Project (2012CB911000; 2010CB912303), the Queensland-Chinese Academy of Sciences Biotechnology Fund (GJHZ1131) and the External Cooperation Program of BIC, Chinese Academy of Sciences (GJHZ201302).
WOS关键词	GLYCOGEN-SYNTHASE KINASE-3-BETA ; ALZHEIMERS-DISEASE ; PROTEIN-TAU ; IN-VITRO ; POSTTRANSLATIONAL MODIFICATIONS ; CEREBROSPINAL-FLUID ; TRANSGENIC ANIMALS ; CROSS-LINKING ; NEURONAL TAU ; PHOSPHORYLATION
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
WOS研究方向	Neurosciences & Neurology
WOS类目	Neurosciences
WOS记录号	WOS:000324918300010
资助机构	973-Project [2012CB911000, 2010CB912303] ; Queensland-Chinese Academy of Sciences Biotechnology Fund [GJHZ1131] ; External Cooperation Program of BIC, Chinese Academy of Sciences [GJHZ201302]
引用统计	被引频次：43[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.psych.ac.cn/handle/311026/10791
专题	脑与认知科学国家重点实验室
通讯作者	He, RQ (reprint author), Chinese Acad Sci, State Key Lab Brain & Cognit Sci, Inst Biophys, 15 Datun Rd, Beijing 100101, Peoples R China.
作者单位	1.Chinese Acad Sci, State Key Lab Brain & Cognit Sci, Inst Biophys, Beijing 100101, Peoples R China 2.Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China 3.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Lu, Yang,He, Hai-Jin,Zhou, Jun,et al. Hyperphosphorylation Results in Tau Dysfunction in DNA Folding and Protection[J]. JOURNAL OF ALZHEIMERS DISEASE,2013,37(3):551-563.
APA	Lu, Yang.,He, Hai-Jin.,Zhou, Jun.,Miao, Jun-Ye.,Lu, Jing.,...&He, RQ .(2013).Hyperphosphorylation Results in Tau Dysfunction in DNA Folding and Protection.JOURNAL OF ALZHEIMERS DISEASE,37(3),551-563.
MLA	Lu, Yang,et al."Hyperphosphorylation Results in Tau Dysfunction in DNA Folding and Protection".JOURNAL OF ALZHEIMERS DISEASE 37.3(2013):551-563.

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