Related Experiment Video

Updated: Sep 4, 2025

Study of Protein-protein Interactions in Autophagy Research
14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

9.2K

Targeting retinoic acid receptor alpha-corepressor interaction activates chaperone-mediated autophagy and protects

Raquel Gomez-Sintes1,2,3, Qisheng Xin1,2,4, Juan Ignacio Jimenez-Loygorri3

  • 1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.

Nature Communications
|July 21, 2022
PubMed

Insights

Scientists developed new drugs that activate chaperone-mediated autophagy, a cellular process that declines with age. These drugs show promise for treating retinal degeneration by restoring this vital cellular defense mechanism.

Area of Science:

  • Cellular Biology
  • Neuroscience
  • Pharmacology

Background:

  • Chaperone-mediated autophagy (CMA) is crucial for cellular defense against protein aggregation and declines with aging.
  • Restoring CMA function has shown therapeutic benefits in genetic models.

Purpose of the Study:

  • To elucidate the mechanism of action for selective CMA activators.
  • To develop orally bioavailable CMA activators with brain penetration for therapeutic applications.

Main Methods:

  • Investigated the molecular mechanism of previously developed CMA activators.
  • Generated novel orally bioavailable CMA activators.
  • Assessed in vivo efficacy in a retinitis pigmentosa mouse model.

Main Results:

  • Identified that CMA activators stabilize the interaction between retinoic acid receptor alpha (a CMA inhibitor) and its co-repressor.
  • Demonstrated that this stabilization leads to selective CMA activation.
  • Showed in vivo activation of CMA and amelioration of retinal degeneration in a mouse model.

Conclusions:

  • Revealed a novel mechanism for pharmacologically targeting CMA activation.
  • Established a potential therapeutic strategy for retinal degeneration by activating CMA.

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