Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.
J Alzheimers Dis. 2018;64(s1):S535-S546. doi: 10.3233/JAD-179942.
Tau protein plays a major role in the pathogenesis of Alzheimer's disease. Despite many decades of intensive research, the cause of the conformational switch that leads to the remodeling of the highly flexible conformational ensemble of intrinsically disordered protein tau into insoluble filaments is still elusive. We show here that truncation of tau may play a causative role in this conformational change, as evidenced by results obtained from in vitro experiments and from transgenic animal models. This conformational change is a common denominator of pathological tau protein assemblies, and a salient drug target. The long-running research of truncated tau has led to the generation of the first active tau vaccine that has entered clinical trials.
tau 蛋白在阿尔茨海默病的发病机制中起着主要作用。尽管经过了几十年的深入研究，但导致高度灵活的无规卷曲蛋白 tau 构象转变为不溶性纤维的构象转换的原因仍难以捉摸。我们在这里表明，tau 的截断可能在这种构象变化中起因果作用，这一点可以从体外实验和转基因动物模型的结果中得到证明。这种构象变化是病理性 tau 蛋白组装的共同特征，也是一个显著的药物靶点。对截断 tau 的长期研究导致了第一个进入临床试验的活性 tau 疫苗的产生。
