AR-7

Description: AR-7 (Atypical Retinoid 7) is a potent and selective retinoic acid receptor alpha (RARalpha) antagonist and an enhancer of the chaperone-mediated autophagy (CMA). CMA is contributory to cellular quality control and the cellular response to stress through the selective degradation of cytosolic proteins in lysosomes. A decrease in CMA activity occurs in aging and in age-related disorders such as neurodegenerative diseases and diabetes. Signaling through RARalpha inhibits CMA. AR7 was identified to significantly activates CMA activity in mouse fibroblasts. A marked increase in CMA-activating potency is found when AR7 and GR1 are combined, supporting their cooperative effect. Treatment with the transcriptional repressor Actinomycin D partially reduces the stimulatory effect of AR7 on CMA, consistent with transcriptional changes contributing to the upregulation of CMA. The chemical enhancement of CMA protects cells from oxidative stress and from proteotoxicity, supporting a potential therapeutic opportunity when reduced CMA contributes to cellular dysfunction and disease.

References: Nat Chem Biol. 2013 Jun; 9(6):374-82.