Bok Eugene, Leem Eunju, Lee Bo-Ram, Lee Ji Min, Yoo Chang Jae, Lee Eun Mi, Kim Jaekwang
Dementia Research Group, Korea Brain Research Institute, Daegu, South Korea.
School of Life Sciences, Kyungpook National University, Daegu, South Korea.
Front Cell Dev Biol. 2021 Apr 30;9:653815. doi: 10.3389/fcell.2021.653815. eCollection 2021.
Abnormal accumulation of misfolded tau aggregates is a pathological hallmark of various tauopathies including Alzheimer's disease (AD). Although tau is a cytosolic microtubule-associated protein enriched in neurons, it is also found in extracellular milieu, such as interstitial fluid, cerebrospinal fluid, and blood. Accumulating evidence showed that pathological tau spreads along anatomically connected areas in the brain through intercellular transmission and templated misfolding, thereby inducing neurodegeneration and cognitive dysfunction. In line with this, the spatiotemporal spreading of tau pathology is closely correlated with cognitive decline in AD patients. Although the secretion and uptake of tau involve multiple different pathways depending on tau species and cell types, a growing body of evidence suggested that tau is largely secreted in a vesicle-free forms. In this regard, the interaction of vesicle-free tau with membrane is gaining growing attention due to its importance for both of tau secretion and uptake as well as aggregation. Here, we review the recent literature on the mechanisms of the tau-membrane interaction and highlights the roles of lipids and proteins at the membrane in the tau-membrane interaction as well as tau aggregation.
错误折叠的tau聚集体异常积累是包括阿尔茨海默病（AD）在内的各种tau蛋白病的病理标志。尽管tau是一种富含于神经元中的胞质微管相关蛋白，但它也存在于细胞外环境中，如间质液、脑脊液和血液中。越来越多的证据表明，病理性tau通过细胞间传递和模板化错误折叠在大脑中沿解剖学连接区域传播，从而导致神经退行性变和认知功能障碍。与此一致的是，tau病理的时空传播与AD患者的认知衰退密切相关。尽管tau的分泌和摄取取决于tau种类和细胞类型而涉及多种不同途径，但越来越多的证据表明，tau主要以无囊泡形式分泌。在这方面，无囊泡tau与膜的相互作用因其对tau分泌、摄取以及聚集的重要性而受到越来越多的关注。在此，我们综述了关于tau与膜相互作用机制的最新文献，并强调了膜上脂质和蛋白质在tau与膜相互作用以及tau聚集过程中的作用。
