单宁酸（TA）是一种天然多酚，由于其抗炎、抗氧化、抗菌、抗肿瘤、抗病毒和神经保护活性，在生物医学领域显示出巨大的潜力。最近的研究表明，液-液相分离（LLPS）与蛋白质聚集密切相关。因此，调节 LLPS 为神经退行性疾病的治疗提供了新的见解。在本研究中，我们研究了TA对阿尔茨海默病相关蛋白tau的LLPS的影响及其潜在机制。我们的研究结果表明，TA 以双相方式影响 tau 的 LLPS，随着 TA 与 tau 摩尔比的增加，最初的促进和随后的抑制。 TA 通过疏水相互作用和氢键的组合来调节 tau 相分离。 TA-tau 和 tau-tau 相互作用之间的平衡被发现与 TA 诱导的 tau 凝聚物的材料特性有关。我们进一步说明，TA 在相分离中的调节活性高度依赖于靶蛋白。这些发现增强了我们对不同条件下驱动 tau LLPS 的力量的理解，并可能有助于未来合理调节蛋白质相变的化合物的识别和优化。版权所有 © 2024。由 Elsevier B.V 出版。

Tannic acid (TA) is a natural polyphenol that shows great potential in the field of biomedicine due to its anti-inflammatory, anti-oxidant, anti-bacterial, anti-tumor, anti-virus, and neuroprotective activities. Recent studies have revealed that liquid-liquid phase separation (LLPS) is closely associated with protein aggregation. Therefore, modulating LLPS offers new insights into the treatment of neurodegenerative diseases. In this study, we investigated the influence of TA on the LLPS of the Alzheimer's-related protein tau and the underlying mechanism. Our findings indicate that TA affects the LLPS of tau in a biphasic manner, with initial promotion and subsequent suppression as the TA to tau molar ratio increases. TA modulates tau phase separation through a combination of hydrophobic interactions and hydrogen bonds. The balance between TA-tau and tau-tau interactions is found to be relevant to the material properties of TA-induced tau condensates. We further illustrate that the modulatory activity of TA in phase separation is highly dependent on the target proteins. These findings enhance our understanding of the forces driving tau LLPS under different conditions, and may facilitate the identification and optimization of compounds that can rationally modulate protein phase transition in the future.Copyright © 2024. Published by Elsevier B.V.