Slingshot-Cofilin activation mediates mitochondrial and synaptic dysfunction via Aβ ligation to β1-integrin conformers.

ABSTRACT: The accumulation of amyloid-β protein (Aβ) is an early event associated with synaptic and mitochondrial damage in Alzheimer's disease (AD). Recent studies have implicated the filamentous actin (F-actin) severing protein, Cofilin, in synaptic remodeling, mitochondrial dysfunction, and AD pathogenesis. However, whether Cofilin is an essential component of the AD pathogenic process and how Aβ impinges its signals to Cofilin from the neuronal surface are unknown. In this study, we found that Aβ42 oligomers (Aβ42O, amyloid-β protein 1-42 oligomers) bind with high affinity to low or intermediate activation conformers of β1-integrin, resulting in the loss of surface β1-integrin and activation of Cofilin via Slingshot homology-1 (SSH1) activation. Specifically, conditional loss of β1-integrin prev

SUBMITTER: Woo JA 

PROVIDER: S-EPMC4423195 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature