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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.<\/jats:p>","DOI":"10.1126\/science.add6696","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T14:02:48Z","timestamp":1690466568000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":99,"title":["TRIM11 protects against tauopathies and is down-regulated in Alzheimer\u2019s disease"],"prefix":"10.1126","volume":"381","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9727-7872","authenticated-orcid":true,"given":"Zi-Yang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cancer Biology and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, 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