Amyloid β production is regulated by β2-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor.

ABSTRACT: Alteration of ryanodine receptor (RyR)-mediated calcium (Ca²⁺) signaling has been reported in Alzheimer disease (AD) models. However, the molecular mechanisms underlying altered RyR-mediated intracellular Ca²⁺ release in AD remain to be fully elucidated. We report here that RyR2 undergoes post-translational modifications (phosphorylation, oxidation, and nitrosylation) in SH-SY5Y neuroblastoma cells expressing the β-amyloid precursor protein (βAPP) harboring the familial double Swedish mutations (APPswe). RyR2 macromolecular complex remodeling, characterized by depletion of the regulatory protein calstabin2, resulted in increased cytosolic Ca²⁺ levels and mitochondrial oxidative stress. We also report a functional interplay between amyloid β (Aβ), β-adrenerg

SUBMITTER: Bussiere R 

PROVIDER: S-EPMC5473221 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature