RyR2-Mediated Ca²⁺ Release and Mitochondrial ROS Generation Partake in the Synaptic Dysfunction Caused by Amyloid β Peptide Oligomers.

ABSTRACT: Amyloid β peptide oligomers (AβOs), toxic aggregates with pivotal roles in Alzheimer's disease, trigger persistent and low magnitude Ca²⁺ signals in neurons. We reported previously that these Ca²⁺ signals, which arise from Ca²⁺ entry and subsequent amplification by Ca²⁺ release through ryanodine receptor (RyR) channels, promote mitochondrial network fragmentation and reduce RyR2 expression. Here, we examined if AβOs, by inducing redox sensitive RyR-mediated Ca²⁺ release, stimulate mitochondrial Ca²⁺-uptake, ROS generation and mitochondrial fragmentation, and also investigated the effects of the antioxidant N-acetyl cysteine (NAC) and the mitochondrial antioxidant EUK-134 on AβOs-induced mitochondrial dysfunction. In a

SUBMITTER: SanMartin CD 

PROVIDER: S-EPMC5403897 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature