Respondek Gesine, Krey Lea, Huber Meret, Pflugrad Henning, Wegner Florian, Höglinger Günter U
Klinik für Neurologie, Medizinische Hochschule Hannover (MHH), Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland.
Standort München, Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), München, Deutschland.
Nervenarzt. 2021 Dec;92(12):1227-1238. doi: 10.1007/s00115-021-01210-0. Epub 2021 Oct 15.
Tau pathology is now considered to be the main cause of a wide spectrum of neurodegenerative diseases, which are collectively referred to as tauopathies. These include primary tauopathies, in which tau plays the main role in the pathogenesis as well as secondary tauopathies, such as Alzheimer's disease, in which amyloid beta also plays a substantial role in the disease process in addition to the tau pathology. Primary tauopathies include progressive supranuclear palsy, corticobasal degeneration, Pick's disease and rare hereditary tauopathies, which are referred to as frontotemporal lobar degeneration with microtubule-associated protein tau (MAPT) mutation. Tauopathies differ from each other pathologically by the affected brain regions and cell types as well as by the biochemical characteristics of the aggregated tau protein. Various tau-centered neuroprotective treatment approaches are currently in preclinical and clinical development. They target different mechanisms, including the reduction of tau expression, inhibition of tau aggregation, dissolution of tau aggregates, improvement of cellular mechanisms to eliminate toxic tau species, stabilization of microtubules and prevention of intercellular tau spreading. This review article gives an overview of tauopathies and the current concepts for the development of disease-modifying treatment.
如今,tau蛋白病变被认为是一系列神经退行性疾病的主要病因,这些疾病统称为tau蛋白病。其中包括原发性tau蛋白病,tau蛋白在其发病机制中起主要作用,以及继发性tau蛋白病,如阿尔茨海默病,除了tau蛋白病变外,淀粉样β蛋白在疾病进程中也起重要作用。原发性tau蛋白病包括进行性核上性麻痹、皮质基底节变性、Pick病以及罕见的遗传性tau蛋白病,后者被称为伴有微管相关蛋白tau(MAPT)突变的额颞叶痴呆。tau蛋白病在病理上的差异在于受影响的脑区和细胞类型,以及聚集的tau蛋白的生化特性。目前,各种以tau蛋白为中心的神经保护治疗方法正处于临床前和临床开发阶段。它们针对不同的机制,包括降低tau蛋白表达、抑制tau蛋白聚集、溶解tau蛋白聚集体、改善细胞机制以清除有毒的tau蛋白、稳定微管以及防止细胞间tau蛋白扩散。这篇综述文章概述了tau蛋白病以及目前疾病修饰治疗的发展概念。