Switch Laboratory, Department of Cellular and Molecular Medicine, KULeuven, Herestraat 49, Box 802, Room 08.683, 3000, Leuven, Belgium.
Switch Laboratory, VIB Center for Brain and Disease Research, Herestraat 49, box 802, room 08.683, 3000, Leuven, Belgium.
Chembiochem. 2018 Dec 4;19(23):2424-2432. doi: 10.1002/cbic.201800288. Epub 2018 Oct 12.
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.
tau 是一种微管相关蛋白，在阿尔茨海默病等一组神经退行性疾病中发挥关键作用，它在大脑中传播，诱导病变。由于具有诱导异常蛋白质构象的相似特征，作为自我放大的一种方法，tau 类似于朊病毒的传播，从而在解剖上相关的途径中传播蛋白质聚集体。人们一直在寻找诱导构象变化的“种子”，这引起了广泛关注；然而，关于 tau 如何在细胞间传播的机制（即“细胞间传播”）知之甚少。在这篇综述中，我们收集了 tau 在大脑中传播的证据，并概述了 tau 可以从神经元中释放以及被摄取的方式。此外，我们还汇集了 tau 传播背后的神经毒性机制。深入了解 tau 的传播机制有助于寻找针对聚集 tau 的多种神经退行性疾病的治疗选择。
