A new Review by DRIVE fellows, Muhammed Kocak, Saba Ezazi Erdi, Guillem Jorba, Inés Maestro, and DRIVE beneficiaries, Judith Farrés, Vladimir Kirkin, Ana Martinez and Ole Pless was published on the 9^th of July 2021 in the journal Autophagy. The Review covers established and novel strategies for modulation of autophagy, from agents acting on the PI3K-AKT-mTOR, AMPK and ULK pathways all the way up to the development of autophagy-targeting chimeras for treating neurodegenerative diseases. Definitely a must-read for all translational autophagy scientists!

Abstract: Macroautophagy/autophagy is an evolutionarily conserved pathway responsible for clearing cytosolic aggregated proteins, damaged organelles or invading microorganisms. Dysfunctional autophagy leads to pathological accumulation of the cargo, which has been linked to a range of human diseases, including neurodegenerative diseases, infectious and autoimmune diseases and various forms of cancer. Cumulative work in animal models, application of genetic tools and pharmacologically active compounds, has suggested the potential therapeutic value of autophagy modulation in disease, as diverse as Huntington, Salmonella infection, or pancreatic cancer. Autophagy activation versus inhibition strategies are being explored, while the role of autophagy in pathophysiology is being studied in parallel. However, the progress of preclinical and clinical development of autophagy modulators has been greatly hampered by the paucity of selective pharmacological agents and biomarkers to dissect their precise impact on various forms of autophagy and cellular responses. Here, we summarize established and new strategies in autophagy-related drug discovery and indicate a path toward establishing a more efficient discovery of autophagy-selective pharmacological agents. With this knowledge at hand, modern concepts for therapeutic exploitation of autophagy might become more plausible.

Link for the Review: https://www.tandfonline.com/doi/10.1080/15548627.2021.1936359