Bassoon contributes to tau-seed propagation and neurotoxicity.
Bassoon contributes to tau-seed propagation and neurotoxicity.
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DOI：
10.1038/s41593-022-01191-6
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发表时间：
2022-12
影响因子：
25
通讯作者：
Lasagna-Reeves, Cristian A.
中科院分区：
文献类型：
--
作者：
Martinez, Pablo;Patel, Henika;You, Yanwen;Jury, Nur;Perkins, Abigail;Lee-Gosselin, Audrey;Taylor, Xavier;You, Yingjian;Di Prisco, Gonzalo Viana;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.
Tau聚集是阿尔茨海默病和其他tau病的一个决定性的组织病理学特征。然而，tau繁殖所涉及的细胞机制仍不清楚。在这里，我们进行了一项无偏见的定量蛋白质组学研究，以确定与这种tau种子特异相互作用的蛋白质。我们发现Bason(BSN)是一种突触前支架蛋白，它是从tau病小鼠模型以及阿尔茨海默病和进行性核上性瘫痪尸检样本中分离出来的tau种子的相互作用因子。我们发现，BSN在小鼠和果蝇的tau病模型中都加剧了tau的种植和毒性，并且BSN的下调减少了tau的扩散和整体疾病的病理，挽救了突触和行为障碍，并减少了脑萎缩。我们的发现提高了人们对tau种子如何通过BSN等相互作用来稳定的理解。抑制tau种子的相互作用是治疗神经退行性疾病的一种潜在的新方法。Martinez等人。鉴定了负责繁殖的tau种子的蛋白质互作组。作者发现突触前蛋白巴松如何与tau种子相互作用，增强其稳定性，并随后产生tau毒性和扩散。
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. Martinez et al. identified the protein interactome of the tau seed responsible for propagation. The authors found how the presynaptic protein Bassoon interacts with the tau seed enhancing its stability and subsequently tau toxicity and spreading.
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影响因子：
16.2
作者：
Karsten, Stanislav L.;Sang, Tzu-Kang;Jackson, George R.
通讯作者：
Jackson, George R.
影响因子：
10.9
作者：
Cardoso, M. Jorge;Leung, Kelvin;Ourselin, Sebastien
通讯作者：
Ourselin, Sebastien
影响因子：
15.1
作者：
Jadhav VS;Lin PBC;Pennington T;Di Prisco GV;Jannu AJ;Xu G;Moutinho M;Zhang J;Atwood BK;Puntambekar SS;Bissel SJ;Oblak AL;Landreth GE;Lamb BT
通讯作者：
Lamb BT
影响因子：
5.7
作者：
Avants BB;Tustison NJ;Song G;Cook PA;Klein A;Gee JC
通讯作者：
Gee JC
影响因子：
16.2
作者：
Lasagna-Reeves CA;de Haro M;Hao S;Park J;Rousseaux MW;Al-Ramahi I;Jafar-Nejad P;Vilanova-Velez L;See L;De Maio A;Nitschke L;Wu Z;Troncoso JC;Westbrook TF;Tang J;Botas J;Zoghbi HY
通讯作者：
Zoghbi HY