{"title":"野生型 tau 在阿尔茨海默病和相关 tau 病中的作用。","authors":"Chih Hung Lo, Jonathan N Sachs","doi":"10.36069/jols/20201201","DOIUrl":null,"url":null,"abstract":"<p><p>Tau oligomers have recently emerged as the principal toxic species in Alzheimer's disease (AD) and tauopathies. Tau oligomers are spontaneously self-assembled soluble tau proteins that are formed prior to fibrils, and they have been shown to play a central role in neuronal cell death and in the induction of neurodegeneration in animal models. As the therapeutic paradigm shifts to targeting toxic tau oligomers, this suggests the focus to study tau oligomerization in species that are less susceptible to fibrillization. While truncated and mutation containing tau as well as the isolated repeat domains are particularly prone to fibrillization, the wild-type (WT) tau proteins have been shown to be resistant to fibril formation in the absence of aggregation inducers. In this review, we will summarize and discuss the toxicity of WT tau both in vitro and in vivo, as well as its involvement in tau oligomerization and cell-to-cell propagation of pathology. Understanding the role of WT tau will enable more effective biomarker development and therapeutic discovery for treatment of AD and tauopathies.</p>","PeriodicalId":87302,"journal":{"name":"Journal of life sciences (Westlake Village, Calif.)","volume":"2 4","pages":"1-17"},"PeriodicalIF":0.0000,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929479/pdf/nihms-1652260.pdf","citationCount":"0","resultStr":"{\"title\":\"The role of wild-type tau in Alzheimer's disease and related tauopathies.\",\"authors\":\"Chih Hung Lo, Jonathan N Sachs\",\"doi\":\"10.36069/jols/20201201\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Tau oligomers have recently emerged as the principal toxic species in Alzheimer's disease (AD) and tauopathies. Tau oligomers are spontaneously self-assembled soluble tau proteins that are formed prior to fibrils, and they have been shown to play a central role in neuronal cell death and in the induction of neurodegeneration in animal models. As the therapeutic paradigm shifts to targeting toxic tau oligomers, this suggests the focus to study tau oligomerization in species that are less susceptible to fibrillization. While truncated and mutation containing tau as well as the isolated repeat domains are particularly prone to fibrillization, the wild-type (WT) tau proteins have been shown to be resistant to fibril formation in the absence of aggregation inducers. In this review, we will summarize and discuss the toxicity of WT tau both in vitro and in vivo, as well as its involvement in tau oligomerization and cell-to-cell propagation of pathology. Understanding the role of WT tau will enable more effective biomarker development and therapeutic discovery for treatment of AD and tauopathies.</p>\",\"PeriodicalId\":87302,\"journal\":{\"name\":\"Journal of life sciences (Westlake Village, Calif.)\",\"volume\":\"2 4\",\"pages\":\"1-17\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2020-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929479/pdf/nihms-1652260.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of life sciences (Westlake Village, Calif.)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.36069/jols/20201201\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of life sciences (Westlake Village, Calif.)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.36069/jols/20201201","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
Tau 低聚物最近已成为阿尔茨海默病(AD)和tau病的主要毒性物质。Tau 寡聚体是一种自发自组装的可溶性 Tau 蛋白,在形成纤维之前就已形成,它们已被证明在动物模型中神经细胞死亡和诱导神经退行性变中发挥了核心作用。随着治疗范式转向靶向毒性 tau 低聚物,这表明研究重点应放在不易纤维化的物种中的 tau 低聚物化。虽然含有截短和突变的 tau 蛋白以及孤立的重复结构域特别容易发生纤维化,但野生型(WT)tau 蛋白已被证明在没有聚集诱导剂的情况下能抵抗纤维的形成。在本综述中,我们将总结并讨论WT tau在体外和体内的毒性,以及它在tau寡聚化和细胞间病理传播中的参与。了解WT tau的作用将有助于更有效地开发生物标记物和发现治疗AD和tau病的疗法。
The role of wild-type tau in Alzheimer's disease and related tauopathies.
Tau oligomers have recently emerged as the principal toxic species in Alzheimer's disease (AD) and tauopathies. Tau oligomers are spontaneously self-assembled soluble tau proteins that are formed prior to fibrils, and they have been shown to play a central role in neuronal cell death and in the induction of neurodegeneration in animal models. As the therapeutic paradigm shifts to targeting toxic tau oligomers, this suggests the focus to study tau oligomerization in species that are less susceptible to fibrillization. While truncated and mutation containing tau as well as the isolated repeat domains are particularly prone to fibrillization, the wild-type (WT) tau proteins have been shown to be resistant to fibril formation in the absence of aggregation inducers. In this review, we will summarize and discuss the toxicity of WT tau both in vitro and in vivo, as well as its involvement in tau oligomerization and cell-to-cell propagation of pathology. Understanding the role of WT tau will enable more effective biomarker development and therapeutic discovery for treatment of AD and tauopathies.