Activation of Microbiota Sensing - Free Fatty Acid Receptor 2 Signaling Ameliorates Amyloid-β Induced Neurotoxicity by Modulating Proteolysis-Senescence Axis.

ABSTRACT: Multiple emerging evidence indicates that the gut microbiota contributes to the pathology of Alzheimer's disease (AD)-a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated, and established the agonists of free fatty acid receptor 2 (FFAR2) signaling, which senses beneficial signals from short chain fatty acids (SCFAs) produced by microbiota. The abundance of SCFAs, is often low in the gut of older adults with AD. We demonstrated that inhibition of FFAR2 signaling increases amyloid-beta (Aβ) stimulated neuronal toxicity. Thus, we screened FFAR2 agonists using an in-silico library of more than 144,000 natural compounds and selected 15 of them bas

SUBMITTER: Razazan A 

PROVIDER: S-EPMC8544178 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature