Tandem detergent-extraction and immunoprecipitation of proteinopathy: Scalable enrichment of ALS-associated TDP-43 aggregates.
Tandem detergent-extraction and immunoprecipitation of proteinopathy: Scalable enrichment of ALS-associated TDP-43 aggregates.
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DOI：
10.1016/j.isci.2023.106645
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发表时间：
2023-05-19
期刊：
影响因子：
5.8
通讯作者：
Cohen, Todd J.
中科院分区：
文献类型：
--
作者：
Evangelista, Baggio A.;Cahalan, Shannon R.;Ragusa, Joey V.;Mordant, Angie;Necarsulmer, Julie C.;Perna, Robert J.;Ajit, Tejazaditya;White, Kristen;Barker, Natalie K.;Tian, Xu;Cohen, Sarah;Meeker, Rick;Herring, Laura E.;Cohen, Todd J.
Transactive response DNA-binding protein of 43 kDa (TDP-43) is a highly conserved, ubiquitously expressed nucleic acid-binding protein that regulates DNA/RNA metabolism. Genetics and neuropathology studies have linked TDP-43 to several neuromuscular and neurological disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Under pathological conditions, TDP-43 mislocalizes to the cytoplasm where it forms insoluble, hyper-phosphorylated aggregates during disease progression. Here, we optimized a scalable in vitro immuno-purification strategy referred to as tandem detergent-extraction and immunoprecipitation of proteinopathy (TDiP) to isolate TDP-43 aggregates that recapitulate those identified in postmortem ALS tissue. Moreover, we demonstrate that these purified aggregates can be utilized in biochemical, proteomics, and live-cell assays. This platform offers a rapid, accessible, and streamlined approach to study ALS disease mechanisms, while overcoming many limitations that have hampered TDP-43 disease modeling and therapeutic drug discovery efforts. TDiP offers scalable purification of TDP-43 aggregates formed in situ TDiP aggregates recapitulate the pathological features of human ALS pathology TDiP aggregates harbor a diverse proteome and seed endogenous TDP-43 TDiP aggregates are suitable for live-cell interaction and trafficking studies Biological sciences; Biochemistry; Molecular biology; Proteomics
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影响因子：
4.6
作者：
Bargsted L;Medinas DB;Martínez Traub F;Rozas P;Muñoz N;Nassif M;Jerez C;Catenaccio A;Court FA;Hetz C;Matus S
通讯作者：
Matus S
FTLD-TDP 组装体通过类似朊病毒的级联产生具有亚型特异性特征的新聚集体。
影响因子：
7.7
作者：
De Rossi P;Lewis AJ;Furrer J;De Vos L;Demeter T;Zbinden A;Zhong W;Wiersma VI;Scialo C;Weber J;Guo Z;Scaramuzza S;Di Fabrizio M;Böing C;Castaño-Díez D;Al-Amoudi A;Pérez-Berlanga M;Lashley T;Stahlberg H;Polymenidou M
通讯作者：
Polymenidou M
影响因子：
16.6
作者：
Cohen, Todd J.;Hwang, Andrew W.;Restrepo, Clark R.;Yuan, Chao-Xing;Trojanowski, John Q.;Lee, Virginia M. Y.
通讯作者：
Lee, Virginia M. Y.
TDP-43 剪接活性需要 N 端二聚化
影响因子：
4.6
作者：
Jiang LL;Xue W;Hong JY;Zhang JT;Li MJ;Yu SN;He JH;Hu HY
通讯作者：
Hu HY
DOI：
10.1021/acs.jpcb.1c00767
发表时间：
2021-04-22
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Shuster SO;Lee JC
通讯作者：
Lee JC