当前位置:科学网首页 > 小柯机器人 >详情
巴松管有助于tau-seed的传播和神经毒性
作者:小柯机器人 发布时间:2022/11/10 14:56:38

美国印第安纳大学医学院Cristian A. Lasagna-Reeves团队近期取得重要工作进展,他们研究发现巴松管(BSN)有助于tau-seed的传播和神经毒性。该项研究成果2022年11月7日在线发表于《自然—神经科学》杂志上。

研究人员进行了无偏差定量蛋白质组学研究,以鉴定与tau seed特异性相互作用的蛋白质。他们发现了巴松管(BSN),一种突触前的支架蛋白,是一种从tau蛋白病小鼠模型以及阿尔茨海默病和进行性核上麻痹死后样本中,分离出来的tau seed的相互作用物。研究人员表明,BSN在小鼠和果蝇的tau蛋白病模型中都会加剧tau的传播和毒性,并且BSN下调会减少tau蛋白传播和整体疾病病理,挽救突触和行为损伤,减少脑萎缩。

这一发现提高了人们对tau seed如何被BSN等相互作用物稳定的认识。抑制tau-seed相互作用是神经退行性tau蛋白病的潜在新治疗方法。

据介绍,tau蛋白聚集是阿尔茨海默病和其他tau蛋白病一个明确的组织病理学特征。然而,参与tau蛋白传播的细胞机制仍不清楚。

附:英文原文

Title: Bassoon contributes to tau-seed propagation and neurotoxicity

Author: Martinez, Pablo, Patel, Henika, You, Yanwen, Jury, Nur, Perkins, Abigail, Lee-Gosselin, Audrey, Taylor, Xavier, You, Yingjian, Viana Di Prisco, Gonzalo, Huang, Xiaoqing, Dutta, Sayan, Wijeratne, Aruna B., Redding-Ochoa, Javier, Shahid, Syed Salman, Codocedo, Juan F., Min, Sehong, Landreth, Gary E., Mosley, Amber L., Wu, Yu-Chien, McKinzie, David L., Rochet, Jean-Christophe, Zhang, Jie, Atwood, Brady K., Troncoso, Juan, Lasagna-Reeves, Cristian A.

Issue&Volume: 2022-11-07

Abstract: Tau aggregation is a defining histopathological feature of Alzheimer’s disease and other tauopathies. However, the cellular mechanisms involved in tau propagation remain unclear. Here, we performed an unbiased quantitative proteomic study to identify proteins that specifically interact with this tau seed. We identified Bassoon (BSN), a presynaptic scaffolding protein, as an interactor of the tau seed isolated from a mouse model of tauopathy, and from Alzheimer’s disease and progressive supranuclear palsy postmortem samples. We show that BSN exacerbates tau seeding and toxicity in both mouse and Drosophila models for tauopathy, and that BSN downregulation decreases tau spreading and overall disease pathology, rescuing synaptic and behavioral impairments and reducing brain atrophy. Our findings improve the understanding of how tau seeds can be stabilized by interactors such as BSN. Inhibiting tau-seed interactions is a potential new therapeutic approach for neurodegenerative tauopathies.

DOI: 10.1038/s41593-022-01191-6

Source: https://www.nature.com/articles/s41593-022-01191-6

期刊信息

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:21.126
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex