| Popis: |
Disruption of neuronal dendrites causes cognitive impairment in Alzheimer’s disease (AD). Rock2, a kinase of the Rho family of proteins, is a dendrite destabilizer that accumulates in the AD brain. However, why Rock2 aberrantly aggregates, causing neuronal integrity loss, is unknown. Here, we show that Rock2 protein stability is controlled by the ubiquitin ligase APC/CCdh1. Accordingly, APC/CCdh1 loss of function in adult neurons increases Rock2 protein and activity, causing dendrite disruption in the cortex and hippocampus, along with memory loss and neurodegeneration, in mice. These effects are abolished by inhibition of Rock2 activity. Thus, the APC/CCdh1-Rock2 pathway may be a novel therapeutic target against neurodegeneration. |
