{"doi":"10.1126/science.add6696","title":"TRIM11 protects against tauopathies and is down-regulated in Alzheimer’s disease","abstract":"Aggregation of tau into filamentous inclusions underlies Alzheimer's disease (AD) and numerous other neurodegenerative tauopathies. The pathogenesis of tauopathies remains unclear, which impedes the development of disease-modifying treatments. Here, by systematically analyzing human tripartite motif (TRIM) proteins, we identified a few TRIMs that could potently inhibit tau aggregation. Among them, TRIM11 was markedly down-regulated in AD brains. TRIM11 promoted the proteasomal degradation of mutant tau as well as superfluous normal tau. It also enhanced tau solubility by acting as both a molecular chaperone to prevent tau misfolding and a disaggregase to dissolve preformed tau fibrils. TRIM11 maintained the connectivity and viability of neurons. Intracranial delivery of TRIM11 through adeno-associated viruses ameliorated pathology, neuroinflammation, and cognitive impairments in multiple animal models of tauopathies. These results suggest that TRIM11 down-regulation contributes to the pathogenesis of tauopathies and that restoring TRIM11 expression may represent an effective therapeutic strategy.","journal":"Science","year":2023,"id":316664,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":96,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":273481,"name":"Dilshan S. Harischandra","orcid":"0000-0003-3220-8765","position":1,"is_corresponding":false},{"id":1020908,"name":"Ruifang Wang","orcid":"0000-0001-8628-6086","position":2,"is_corresponding":false},{"id":343957,"name":"Shivani Ghaisas","orcid":"0000-0001-7827-8190","position":3,"is_corresponding":false},{"id":1020909,"name":"Janet Yinqing Zhao","orcid":"0000-0002-5489-4172","position":4,"is_corresponding":false},{"id":1021805,"name":"Thomas P. McMonagle","orcid":null,"position":5,"is_corresponding":false},{"id":92380,"name":"Guixin Zhu","orcid":"0000-0001-9619-9437","position":6,"is_corresponding":false},{"id":1020910,"name":"Kenzo D. Lacuarta","orcid":"0009-0004-8555-6178","position":7,"is_corresponding":false},{"id":1020911,"name":"Jianing Song","orcid":"0000-0003-0623-0395","position":8,"is_corresponding":false},{"id":27606,"name":"John Q. Trojanowski","orcid":"0000-0002-9239-8794","position":9,"is_corresponding":false},{"id":275982,"name":"Hong Xu","orcid":"0000-0002-3501-4758","position":10,"is_corresponding":false},{"id":27604,"name":"Virginia M.‐Y. Lee","orcid":"0000-0003-3536-6902","position":11,"is_corresponding":false},{"id":236725,"name":"Xiaolu Yang","orcid":"0000-0001-6755-7725","position":12,"is_corresponding":false},{"id":1020907,"name":"Z. Zhang","orcid":"0009-0007-9727-7872","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-19T01:06:44.698773Z","pmid":"37499037","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}