Orr Miranda E, Sullivan A Campbell, Frost Bess
Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Pharmacology, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
Department of Neurology, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
Trends Pharmacol Sci. 2017 Jul;38(7):637-648. doi: 10.1016/j.tips.2017.03.011. Epub 2017 Apr 25.
There are currently no disease-modifying therapies for the treatment of tauopathies, a group of progressive neurodegenerative disorders that are pathologically defined by the presence of tau protein aggregates in the brain. Current challenges for the treatment of tauopathies include the inability to diagnose early and to confidently discriminate between distinct tauopathies in patients, alongside an incomplete understanding of the cellular mechanisms involved in pathogenic tau-induced neuronal death and dysfunction. In this review, we describe current diagnostic and therapeutic strategies, known drivers of pathogenic tau formation, recent contributions to our current mechanistic understanding of how pathogenic tau induces neuronal death, and potential diagnostic and therapeutic approaches.
目前尚无用于治疗tau蛋白病的疾病修饰疗法,tau蛋白病是一组进行性神经退行性疾病,在病理学上由大脑中tau蛋白聚集体的存在来定义。tau蛋白病治疗目前面临的挑战包括无法早期诊断以及难以在患者中准确区分不同的tau蛋白病,同时对致病性tau蛋白诱导神经元死亡和功能障碍所涉及的细胞机制了解不全面。在本综述中,我们描述了当前的诊断和治疗策略、已知的致病性tau蛋白形成驱动因素、对我们目前关于致病性tau蛋白如何诱导神经元死亡的机制理解的最新贡献,以及潜在的诊断和治疗方法。