| First Author | Zhang ZY | Year | 2023 |
| Journal | Science | Volume | 381 |
| Issue | 6656 | Pages | eadd6696 |
| PubMed ID | 37499037 | Mgi Jnum | J:339456 |
| Mgi Id | MGI:7522541 | Doi | 10.1126/science.add6696 |
| Citation | Zhang ZY, et al. (2023) TRIM11 protects against tauopathies and is down-regulated in Alzheimer's disease. Science 381(6656):eadd6696 |
| abstractText | 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. |
