Somatostatin-evoked Aβ catabolism in the brain: Mechanistic involvement of α-endosulfine-K_ATP channel pathway.

ABSTRACT: Alzheimer's disease (AD) is characterized by the deposition of amyloid β peptide (Aβ) in the brain. The neuropeptide somatostatin (SST) regulates Aβ catabolism by enhancing neprilysin (NEP)-catalyzed proteolytic degradation. However, the mechanism by which SST regulates NEP activity remains unclear. Here, we identified α-endosulfine (ENSA), an endogenous ligand of the ATP-sensitive potassium (K_ATP) channel, as a negative regulator of NEP downstream of SST signaling. The expression of ENSA is significantly increased in AD mouse models and in patients with AD. In addition, NEP directly contributes to the degradation of ENSA, suggesting a substrate-dependent feedback loop regulating NEP activity. We also discovered the specific K_ATP channel subtype that modulates NEP act

SUBMITTER: Watamura N 

PROVIDER: S-EPMC9095489 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature