Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA.
Science. 2021 Feb 26;371(6532). doi: 10.1126/science.abb8255.
Several lines of evidence implicate the protein tau in the pathogenesis of multiple brain disorders, including Alzheimer's disease, other neurodegenerative conditions, autism, and epilepsy. Tau is abundant in neurons and interacts with microtubules, but its main functions in the brain remain to be defined. These functions may involve the regulation of signaling pathways relevant to diverse biological processes. Informative disease models have revealed a plethora of abnormal tau species and mechanisms that might contribute to neuronal dysfunction and loss, but the relative importance of their respective contributions is uncertain. This knowledge gap poses major obstacles to the development of truly impactful therapeutic strategies. The current expansion and intensification of efforts to translate mechanistic insights into tau-related therapeutics should address this issue and could deliver better treatments for a host of devastating conditions.
有几条证据表明蛋白 tau 与多种脑部疾病的发病机制有关,包括阿尔茨海默病、其他神经退行性疾病、自闭症和癫痫。Tau 在神经元中含量丰富,并与微管相互作用,但它在大脑中的主要功能仍有待确定。这些功能可能涉及调节与多种生物过程相关的信号通路。有启发性的疾病模型揭示了大量异常的 tau 物种和机制,这些可能导致神经元功能障碍和丧失,但它们各自的贡献的相对重要性尚不确定。这一知识空白给真正有影响力的治疗策略的发展带来了重大障碍。目前,将机制见解转化为与 tau 相关的治疗方法的努力正在扩大和加强,应该解决这个问题,并为许多毁灭性疾病带来更好的治疗方法。