Behind the curtain of tauopathy: a show of multiple players orchestrating tau toxicity

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• 作者：Yunpeng Huang ; Zhihao Wu ; Bing Zhou
• 关键词：Hyperphosphorylation ; Zinc ; Chaperon ; Degradation ; Therapeutic strategy
• 刊名：Cellular and Molecular Life Sciences (CMLS)
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：73
• 期：1
• 页码：1-21
• 全文大小：1,061 KB
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• 作者单位：Yunpeng Huang (1)
  Zhihao Wu (2)
  Bing Zhou (1) (3)
  
  1. State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing, 100084, China
  2. Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA
  3. Beijing Institute for Brain Disorders, Beijing, China
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Biomedicine
  Life Sciences
  Biochemistry
  
• 出版者：Birkh盲user Basel
• ISSN：1420-9071

文摘

tau, a microtubule-associated protein, directly binds with microtubules to dynamically regulate the organization of cellular cytoskeletons, and is especially abundant in neurons of the central nervous system. Under disease conditions such as Pick’s disease, progressive supranuclear palsy, frontotemporal dementia, parkinsonism linked to chromosome 17 and Alzheimer’s disease, tau proteins can self-assemble to paired helical filaments progressing to neurofibrillary tangles. In these diseases, collectively referred to as “tauopathies”, alterations of diverse tau modifications including phosphorylation, metal ion binding, glycosylation, as well as structural changes of tau proteins have all been observed, indicating the complexity and variability of factors in the regulation of tau toxicity. Here, we review our current knowledge and hypotheses from relevant studies on tau toxicity, emphasizing the roles of phosphorylations, metal ions, folding and clearance control underlining tau etiology and their regulations. A summary of clinical efforts and associated findings of drug candidates under development is also presented. It is hoped that a more comprehensive understanding of tau regulation will provide us with a better blueprint of tau networking in neuronal cells and offer hints for the design of more efficient strategies to tackle tau-related diseases in the future. Keywords Hyperphosphorylation Zinc Chaperon Degradation Therapeutic strategy