Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.07.329318v1?rss=1 Authors: Watamura, N., Kakiya, N., Nilsson, P., Tsubuki, S., Kamano, N., Takahashi, M., Hashimoto, S., Sasaguri, H., Saito, T., Saido, T. Abstract: The neuropeptide somatostatin (SST) regulates amyloid {beta} peptide (A{beta}) catabolism by enhancing neprilysin (NEP)-catalyzed proteolytic degradation. However, the mechanism by which SST regulates NEP activity remains unclear. Here we report the identification by differential proteomics of -endosulfine (ENSA), an endogenous ligand of the ATP-sensitive potassium (KATP) channel, as a negative regulator of NEP activity downstream of SST signaling. Genetic deficiency of ENSA resulted in enhanced NEP activity and decreased A{beta} deposition in the brains of wild-type and Alzheimer's disease (AD) model mice. Pharmacological intervention to increase the probability of KATP channel opening reduced A{beta} deposition in AD model mice. Our findings provide new insights into possible mechanisms to prevent AD. Copy rights belong to original authors. Visit the link for more info