Seitkazina Assel, Kim Kyu Hyeon, Fagan Erin, Sung Yoonsik, Kim Yun Kyung, Lim Sungsu
Convergence Research Center for Brain Science, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea.
Division of Bio-Medical Science and Technology, Korea Institute of Science and Technology (KIST) School, University of Science and Technology (UST), Seoul, South Korea.
Front Aging Neurosci. 2022 Jul 18;14:932541. doi: 10.3389/fnagi.2022.932541. eCollection 2022.
Neuronal accumulation of mis-folded tau is the pathological hallmark of multiple neurodegenerative disorders, including Alzheimer's disease. Distinct from amyloid plaques, which appear simultaneously throughout the brain, tau pathology develops first in a specific brain region and then propagates to neuroanatomically connected brain regions, exacerbating the disease. Due to the implication in disease progression, prevention of tau transmission is recognized as an important therapeutic strategy that can halt disease progression in the brain. Recently, accumulating studies have demonstrated diverse cellular mechanisms associated with cell-to-cell transmission of tau. Once transmitted, mis-folded tau species act as a prion-like seed for native tau aggregation in the recipient neuron. In this review, we summarize the diverse cellular mechanisms associated with the secretion and uptake of tau, and highlight tau-trafficking receptors, which mediate tau clearance or cell-to-cell tau transmission.
错误折叠的tau蛋白在神经元中的积累是包括阿尔茨海默病在内的多种神经退行性疾病的病理标志。与在整个大脑中同时出现的淀粉样斑块不同，tau蛋白病变首先在特定脑区出现，然后传播到神经解剖学上相连的脑区，从而加剧疾病。由于其与疾病进展相关，预防tau蛋白传播被认为是一种重要的治疗策略，可阻止大脑中的疾病进展。最近，越来越多的研究表明了与tau蛋白细胞间传播相关的多种细胞机制。一旦传播，错误折叠的tau蛋白种类就会作为朊病毒样种子，引发受体神经元中天然tau蛋白的聚集。在这篇综述中，我们总结了与tau蛋白分泌和摄取相关的多种细胞机制，并强调了介导tau蛋白清除或细胞间tau蛋白传播的tau蛋白转运受体。
