John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Lancet Neurol. 2013 Jun;12(6):609-22. doi: 10.1016/S1474-4422(13)70090-5.
The pathway leading from soluble and monomeric to hyperphosphorylated, insoluble and filamentous tau protein is at the centre of many human neurodegenerative diseases, collectively referred to as tauopathies. Dominantly inherited mutations in MAPT, the gene that encodes tau, cause forms of frontotemporal dementia and parkinsonism, proving that dysfunction of tau is sufficient to cause neurodegeneration and dementia. However, most cases of tauopathy are not inherited in a dominant manner. The first tau aggregates form in a few nerve cells in discrete brain areas. These become self propagating and spread to distant brain regions in a prion-like manner. The prevention of tau aggregation and propagation is the focus of attempts to develop mechanism-based treatments for tauopathies.
从可溶性单体到过度磷酸化、不溶性丝状的 tau 蛋白的途径是许多人类神经退行性疾病的核心，这些疾病统称为 tau 病。MAPT 基因（编码 tau 蛋白）的显性遗传突变导致额颞叶痴呆和帕金森病，证明 tau 蛋白功能障碍足以导致神经退行性变和痴呆。然而，大多数 tau 病不是以显性方式遗传的。第一个 tau 聚集物首先在离散脑区的少数神经细胞中形成。这些 tau 聚集物以类朊病毒的方式自我传播，并扩散到遥远的脑区。tau 聚集和传播的预防是开发 tau 病基于机制的治疗方法的重点。
