Drug discovery by targeting the protein-protein interactions involved in autophagy

Autophagy is a cellular process in which proteins and organelles are engulfed in autophago-somal vesicles and transported to the lysosome/vacuole for degradation. Protein-protein interactions (PPIs) play a crucial role at many stages of autophagy, which present formidable but attainable targets for autophagy regulation. Moreover, selective regulation of PPIs tends to have a lower risk in causing undesired off-target effects in the context of a complicated biological network. Thus, small-molecule reg-ulators, including peptides and peptidomimetics, targeting the critical PPIs involved in autophagy provide a new opportunity for innovative drug discovery. This article provides general background knowledge of the critical PPIs involved in autophagy and reviews a range of successful attempts on discovering regu-lators targeting those PPIs. Successful strategies and existing limitations in this field are also discussed.(c) 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Autophagy is a cellular process that involves the engulfment and degradation of proteins and organelles through protein-protein interactions. Targeting selective regulation of these interactions provides a new opportunity for autophagy regulation with lower risk of off-target effects. This article provides background knowledge on critical protein-protein interactions in autophagy and reviews successful attempts in discovering regulators targeting these interactions. It also discusses successful strategies and existing limitations in this field.