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	Tumor-suppressor PTEN affects tau phosphorylation, aggregation, and binding to microtubules
	Zhang, X. ; Li, F. ; Bulloj, A. ; Zhang, Y. W. ; Tong, G. ; Zhang, Z. ; Liao, F. F. ; Xu, H. ; Zhang YW(张云武)
	2006
关键词	Alzheimer's disease tauopathy PIP3/Akt
英文摘要	Neurofibrillary tangles (NFTs), consisting of abnormally hyperphosphorylated tau, are implicated in the pathogenesis of several neurodegenerative diseases including Alzheimer's disease (AD). The molecular mechanisms underlying the regulation of tau phosphorylation are largely unknown. While the PI3K/ Akt pathway has been shown to regulate multiple cellular events pertinent to AD pathogenesis, potential functions of tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in AD pathogenesis have not been explored. Here, we examine the effects of PTEN on tau phosphorylation, its microtubule association and formation of aggregates, and consequentially neuronal morphology. In cultured cells, overexpression of wild-type (WT) PTEN alters tau phosphorylation at several sites, increases tau-microtubule association and decreases formation of tau aggregates. In addition, the phosphatase-null PTEN increases tau aggregation and impairs tau binding to microtubule and neurite outgrowth of neurons expressing the mutant PTEN. We also found a significant loss of PTEN in AD patient brains correlated with a dramatically increased concentration of phospho-tau at Ser-214 in NFTs. Together, our results demonstrate that PTEN regulates tau phosphorylation, binding to micro-tubules and formation of aggregates and neurite outgrowth. These findings suggest a link between malfunction of PTEN and tauopathy, and imply PTEN as a therapeutic target for tauopathy.-Zhang, X., Li, F., Bulloj, A., Zhang, Y.-w., Tong, G., Zhang, Z., Liao, F.-F., Xu, H. Tumor-suppressor PTEN affects tau phosphorylation, aggregation, and binding to microtubules.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/66009]
专题	生物医学－已发表论文
推荐引用方式 GB/T 7714	Zhang, X.,Li, F.,Bulloj, A.,et al. Tumor-suppressor PTEN affects tau phosphorylation, aggregation, and binding to microtubules[J],2006.
APA	Zhang, X..,Li, F..,Bulloj, A..,Zhang, Y. W..,Tong, G..,...&张云武.(2006).Tumor-suppressor PTEN affects tau phosphorylation, aggregation, and binding to microtubules..
MLA	Zhang, X.,et al."Tumor-suppressor PTEN affects tau phosphorylation, aggregation, and binding to microtubules".(2006).

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