Transcellular Spreading of Tau in Tauopathies.
Transcellular Spreading of Tau in Tauopathies.
复制标题
tau在tauopathies中的跨细胞扩散。
DOI：
10.1002/cbic.201800288
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发表时间：
2018-12-04
期刊：
影响因子：
--
通讯作者：
Rousseau F
中科院分区：
文献类型：
--
作者：
Demaegd K;Schymkowitz J;Rousseau F
Tau是一种微管相关蛋白，在一组神经退行性疾病（如阿尔茨海默病）中发挥关键作用，它遍布大脑，诱导病理学。由于诱导异常蛋白质构象作为自我扩增方法的相似特征，已经提出了类似于朊病毒传播的模型，将蛋白质聚集体传播到解剖学上连接的途径上。识别诱导构象变化的“种子”的研究受到了广泛关注;然而，关于tau从细胞到细胞的传递机制，即所谓的“跨细胞传播”，人们知之甚少。在这篇综述中，我们收集了关于tau在整个大脑中传播的证据，并概述了tau可以从神经元释放和吸收的方法。此外，我们将tau蛋白扩散背后的神经毒性机制结合在一起。推进我们对tau扩散的理解可以指导寻找聚集tau的多种神经退行性疾病的治疗选择。
Tau, a microtubule‐associated protein playing a key role in a group of neurodegenerative diseases such as Alzheimer's disease, spreads throughout the brain, inducing pathology. A model akin to the spreading of prions has been raised owing to similar characteristics of inducing an abnormal protein conformation as a method of self‐amplification, spreading protein aggregates over anatomically linked pathways. The search to identify the “seeds” that induce conformational change has received much attention; however, less is known about the mechanisms by which tau is transmitted from cell to cell, so‐called “transcellular spreading”. In this review, we gather evidence regarding the spreading of tau throughout the brain and provide an overview of methods by which tau can be released from neurons as well as taken up. Furthermore, we bring together mechanisms of neurotoxicity behind tau spreading. Advancing our understanding about the spreading of tau can guide the search for therapeutic options for multiple neurodegenerative diseases aggregating tau.
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