MRC Laboratory of Molecular Biology, Cambridge, UK.
FEBS Lett. 2018 Jul;592(14):2383-2391. doi: 10.1002/1873-3468.13108. Epub 2018 Jul 6.
The ordered assembly of Tau protein into abnormal filamentous inclusions is a defining characteristic of many human neurodegenerative diseases. Thirty years ago, we reported that Tau is an integral component of the intraneuronal filaments of Alzheimer's disease. All six brain Tau isoforms make up those filaments. Twenty years ago, we and others showed that mutations in MAPT, the Tau gene, cause familial forms of frontotemporal dementia, thus proving that dysfunction of Tau protein is sufficient to cause neurodegeneration and dementia. More recently, we showed that high-resolution structures of Tau filaments from human brain can be determined by electron cryo-microscopy. These filaments may form the seeds that underlie the prion-like properties of aggregated tau.
Tau 蛋白有序组装成异常纤维状包含物是许多人类神经退行性疾病的特征。三十年前，我们报道了 Tau 是阿尔茨海默病神经元内纤维的组成部分。六种脑 Tau 异构体共同构成了这些纤维。二十年前，我们和其他人证明 MAPT（Tau 基因）的突变导致额颞叶痴呆的家族形式，从而证明 Tau 蛋白功能障碍足以导致神经退行性变和痴呆。最近，我们表明，可以通过电子冷冻显微镜确定来自人脑的 Tau 纤维的高分辨率结构。这些纤维可能形成了聚集 Tau 蛋白具有类朊病毒特性的基础种子。
