麻省总医院神经退行性疾病研究所Rudolph E. Tanzi课题组的一项最新研究开发出了磷酸化的tau蛋白表现出抗菌活性，能够中和人类神经元中单纯疱疹病毒1的感染性。相关论文于2025年12月17日发表在《自然—神经科学》杂志上。

研究人员之前的研究表明，老年斑的主要成分β淀粉样蛋白（Aβ）是一种能够结合和捕获微生物病原体的抗菌肽。

在这里，该课题组研究人员发现tau蛋白在神经元中对病毒感染的反应是过度磷酸化的，并且可以通过直接结合病毒衣壳来中和单纯疱疹病毒1号（HSV-1）的传染性。他们的数据表明，tau蛋白过度磷酸化、微管不稳定和聚集的“致病性”特征是抗病毒反应的一部分，其中tau蛋白在大脑的先天免疫系统中充当宿主防御蛋白。Aβ和磷酸化tau的联合抗菌活性导致Aβ斑块和神经原纤维缠结，以及神经炎症，表明AD神经病理学可能已经进化为大脑中针对微生物感染的精心安排的先天免疫宿主防御反应。

据悉，Tau是一种微管相关的细胞骨架蛋白，当其过度磷酸化和聚集时，可导致无数不同的Tau病，包括阿尔茨海默病（AD）。

附：英文原文

Title: Phosphorylated tau exhibits antimicrobial activity capable of neutralizing herpes simplex virus 1 infectivity in human neurons

Author: Eimer, William A., Rodriguez, Alex S., DeFao, Michael T., Ehricke, Simon, Park, Joseph, Vijaya Kumar, Deepak K., Navalpur Shanmugam, Nanda K., Singh, Sanjana, Sawhney, Tara, Moir, Robert D., Tanzi, Rudolph E.

Issue&Volume: 2025-12-17

Abstract: Tau is a microtubule-associated cytoskeletal protein, which, when hyperphosphorylated and aggregated, can result in a myriad of different tauopathies, including Alzheimer’s disease (AD). We previously showed that the principal component of senile plaques, amyloid beta (Aβ), is an antimicrobial peptide capable of binding and entrapping microbial pathogens. Here we show that tau is hyperphosphorylated in neurons in response to viral infection and can neutralize herpes simplex virus 1 (HSV-1) infectivity by directly binding to viral capsids. Our data suggest that the ‘pathogenic’ characteristics of tau hyperphosphorylation, microtubule destabilization and aggregation are part of an antiviral response, in which tau serves as a host defense protein in the innate immune system of the brain. The combined antimicrobial activities of Aβ and phosphorylated tau resulting in Aβ plaques and neurofibrillary tangles, along with neuroinflammation, suggest that AD neuropathology may have evolved as an orchestrated innate immune host defense response to microbial infection in the brain.

DOI: 10.1038/s41593-025-02157-0

Source: https://www.nature.com/articles/s41593-025-02157-0