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bioRxiv · 10.1101/2020.10.07.329318

α-Endosulfine regulates amyloid β42 via the modulation of neprilysin activity

Watamura, N.·Kakiya, N.·Nilsson, P.·Tsubuki, S.·Kamano, N.·Takahashi, M.·Hashimoto, S.·Sasaguri, H.·Saito, T.·Saido, T.
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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 Alzheimers 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.

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Watamura, N., Kakiya, N., Nilsson, P., Tsubuki, S., Kamano, N., Takahashi, M., Hashimoto, S., Sasaguri, H., Saito, T., Saido, T.. 2020-10-08. α-Endosulfine regulates amyloid β42 via the modulation of neprilysin activity. https://doi.org/10.1101/2020.10.07.329318

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