美国贝勒医学院Hugo J. Bellen小组发现，Tau是胶质细胞脂质滴形成和神经元抗氧化应激所需的。这一研究成果于2024年8月26日在线发表在国际学术期刊《自然—神经科学》上。

研究人员表示，活性氧（ROS）的积累是Tau蛋白相关疾病的一个共同特征，这些疾病由神经元和胶质细胞中的Tau积累定义。神经元中的高ROS水平导致脂质的产生和有毒过氧化脂质（LPO）的排出。胶质细胞摄取这些LPO，并将其储存和分解为脂质滴（LD）。

研究人员发现，在果蝇和大鼠神经元-星形胶质细胞共培养物中，过表达Tau会破坏LD，使胶质细胞对有毒的神经元LPO更为敏感。通过使用一个新的果蝇tau功能缺失等位基因和RNA介导的干扰，研究人员发现内源性Tau对胶质细胞LD形成和对抗神经元LPO的保护是必要的。

同样，内源性Tau在大鼠星形胶质细胞和人类类寡突胶质细胞样细胞中也对LD形成和LPO的分解是必需的。从行为学上看，缺乏胶质Tau的果蝇寿命缩短且运动缺陷，这些缺陷可以通过给予抗氧化剂N-乙酰半胱氨酸酰胺得到改善。总体而言，这项工作提供了Tau在胶质细胞中减轻大脑ROS的重要作用的见解。

附：英文原文

Title: Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress

Author: Goodman, Lindsey D., Ralhan, Isha, Li, Xin, Lu, Shenzhao, Moulton, Matthew J., Park, Ye-Jin, Zhao, Pinghan, Kanca, Oguz, Ghaderpour Taleghani, Ziyaneh S., Jacquemyn, Julie, Shulman, Joshua M., Ando, Kanae, Sun, Kai, Ioannou, Maria S., Bellen, Hugo J.

Issue&Volume: 2024-08-26

Abstract: The accumulation of reactive oxygen species (ROS) is a common feature of tauopathies, defined by Tau accumulations in neurons and glia. High ROS in neurons causes lipid production and the export of toxic peroxidated lipids (LPOs). Glia uptake these LPOs and incorporate them into lipid droplets (LDs) for storage and catabolism. We found that overexpressing Tau in glia disrupts LDs in flies and rat neuron–astrocyte co-cultures, sensitizing the glia to toxic, neuronal LPOs. Using a new fly tau loss-of-function allele and RNA-mediated interference, we found that endogenous Tau is required for glial LD formation and protection against neuronal LPOs. Similarly, endogenous Tau is required in rat astrocytes and human oligodendrocyte-like cells for LD formation and the breakdown of LPOs. Behaviorally, flies lacking glial Tau have decreased lifespans and motor defects that are rescuable by administering the antioxidant N-acetylcysteine amide. Overall, this work provides insights into the important role that Tau has in glia to mitigate ROS in the brain.

DOI: 10.1038/s41593-024-01740-1

Source: https://www.nature.com/articles/s41593-024-01740-1