Human TAU(P301L) overexpression results in TAU hyperphosphorylation without neurofibrillary tangles in adult zebrafish brain

doi:10.1038/s41598-017-13311-5

	Human TAU(P301L) overexpression results in TAU hyperphosphorylation without neurofibrillary tangles in adult zebrafish brain
	Cosacak, Mehmet I.1; Bhattarai, Prabesh 1; Bocova, Ledio 1; Dzewas, Tim 1; Mashkaryan, Violeta 1,2; Papadimitriou, Christos 1; Brandt, Kerstin 1; Hollak, Heike 1; Antos, Christopher L.3 ; Kizil, Caghan 1,2
	2017-10-11
发表期刊	SCIENTIFIC REPORTS (IF:3.8[JCR-2023],4.3[5-Year])
ISSN	2045-2322
卷号	7
发表状态	已发表
DOI	10.1038/s41598-017-13311-5
摘要	Microtubule-associated TAU protein is a pathological hallmark in Alzheimer's disease (AD), where hyperphosphorylation of TAU generates neurofibrillary tangles. To investigate the effects of TAU in a regenerative adult vertebrate brain system, we generated a cre/lox-based transgenic model of zebrafish that chronically expresses human TAU(P301L), which is a variant of human TAU protein that forms neurofibrillary tangles in mouse models and humans. Interestingly, we found that although chronic and abundant expression of TAU(P301L) starting from early embryonic development led to hyperphosphorylation, TAU(P301L) did not form oligomers and neurofibrillary tangles, and did not cause elevated apoptosis and microglial activation, which are classical symptoms of tauopathies in mammals. Additionally, TAU(P301L) neither increased neural stem cell proliferation nor activated the expression of regenerative factor Interleukin-4, indicating that TAU(P301L) toxicity is prevented in the adult zebrafish brain. By combining TAU(P301L) expression with our established A beta 42 toxicity model, we found that A beta 42 ceases to initiate neurofibrillary tangle formation by TAU(P301L), and TAU(P301L) does not exacerbate the toxicity of A beta 42. Therefore, our results propose a cellular mechanism that protects the adult zebrafish brain against tauopathies, and our model can be used to understand how TAU toxicity can be prevented in humans.
收录类别	SCI
语种	英语
资助项目	Deutsche Forschungsgemeinschaft (DFG)[KI 1524/6-1]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000412781300027
出版者	NATURE PUBLISHING GROUP
WOS关键词	ALZHEIMERS-DISEASE ; AMYLOID-BETA ; TRANSGENIC ZEBRAFISH ; A-BETA ; REGENERATIVE NEUROGENESIS ; STEM-CELLS ; MODEL ; INFLAMMATION ; PATHOLOGY ; PHOSPHORYLATION
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/9878
专题	生命科学与技术学院生命科学与技术学院_PI研究组_Christopher Lee Antos组
通讯作者	Kizil, Caghan
作者单位	1.German Ctr Neurodegenerat Dis DZNE, Arnoldstr 18, D-01307 Dresden, Germany 2.Tech Univ Dresden, CRTD, Fetscherstr 105, D-01307 Dresden, Germany 3.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Cosacak, Mehmet I.,Bhattarai, Prabesh,Bocova, Ledio,et al. Human TAU(P301L) overexpression results in TAU hyperphosphorylation without neurofibrillary tangles in adult zebrafish brain[J]. SCIENTIFIC REPORTS,2017,7.
APA	Cosacak, Mehmet I..,Bhattarai, Prabesh.,Bocova, Ledio.,Dzewas, Tim.,Mashkaryan, Violeta.,...&Kizil, Caghan.(2017).Human TAU(P301L) overexpression results in TAU hyperphosphorylation without neurofibrillary tangles in adult zebrafish brain.SCIENTIFIC REPORTS,7.
MLA	Cosacak, Mehmet I.,et al."Human TAU(P301L) overexpression results in TAU hyperphosphorylation without neurofibrillary tangles in adult zebrafish brain".SCIENTIFIC REPORTS 7(2017).