胞浆
Tau病理学
抗体
免疫疗法
泛素连接酶
细胞生物学
受体
神经科学
疾病
化学
生物
免疫学
医学
泛素
阿尔茨海默病
生物化学
免疫系统
病理
酶
基因
作者
Aamir S. Mukadam,Lauren V. C. Miller,Annabel E. Smith,Marina Vaysburd,Siri Aastedatter Sakya,Sophie Sanford,Sophie Keeling,Benjamin J. Tuck,Panagiotis Katsinelos,Christopher Green,Lise R. Skov,Sanne S. Kaalund,Stian Foss,Keith Mayes,Kevin O’Connell,Mark Wing,Claire Knox,Jessica Banbury,Edward Avezov,James B. Rowe
出处
期刊:Science
[American Association for the Advancement of Science]
日期:2023-03-31
卷期号:379 (6639): 1336-1341
被引量:43
标识
DOI:10.1126/science.abn1366
摘要
Aggregates of the protein tau are proposed to drive pathogenesis in neurodegenerative diseases. Tau can be targeted by using passively transferred antibodies (Abs), but the mechanisms of Ab protection are incompletely understood. In this work, we used a variety of cell and animal model systems and showed that the cytosolic Ab receptor and E3 ligase TRIM21 (T21) could play a role in Ab protection against tau pathology. Tau-Ab complexes were internalized to the cytosol of neurons, which enabled T21 engagement and protection against seeded aggregation. Ab-mediated protection against tau pathology was lost in mice that lacked T21. Thus, the cytosolic compartment provides a site of immunotherapeutic protection, which may help in the design of Ab-based therapies in neurodegenerative disease.
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