{Reference Type}: Journal Article
{Title}: Cofilin promotes tau pathology in Alzheimer's disease.
{Author}: Yan M;Tang L;Dai L;Lei C;Xiong M;Zhang X;He M;Tian Y;Xiong J;Ke W;Zhang Z;Zhang C;Deng X;Zhang Z;
{Journal}: Cell Rep
{Volume}: 42
{Issue}: 2
{Year}: 02 2023 28
暂无{DOI}: 10.1016/j.celrep.2023.112138
{Abstract}: 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.