| First Author | Yan M | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 2 | Pages | 112138 |
| PubMed ID | 36807141 | Mgi Jnum | J:355373 |
| Mgi Id | MGI:7441810 | Doi | 10.1016/j.celrep.2023.112138 |
| Citation | Yan M, et al. (2023) Cofilin promotes tau pathology in Alzheimer's disease. Cell Rep 42(2):112138 |
| abstractText | The molecular mechanisms mediating the aggregation and transmission of tau in AD remain unclear. Here, we show that the actin-binding protein cofilin is cleaved by a cysteine protease asparagine endopeptidase (AEP) at N138 in the brains of patients with AD. The AEP-generated cofilin 1-138 fragment interacts with tau and promotes its aggregation. The mixed fibrils consisting of cofilin 1-138 and tau are more pathogenic to cells than pure tau fibrils. Furthermore, overexpression of cofilin 1-138 in the brain facilitates the propagation of pathological tau aggregates and promotes AD-like cognitive impairments in tau P301S mice. However, mice infected with adeno-associated viruses (AAVs) encoding an AEP-uncleavable cofilin mutant show attenuated tau pathology and cognitive impairments compared with mice injected with AAVs encoding wild-type cofilin. Together, these observations support the role of the cofilin 1-138 fragment in the aggregation and transmission of tau pathology during the onset and progression of AD. |
