Novel pharmacological modulators of autophagy and therapeutic prospects

Abstract

Introduction: Autophagy is an intracellular process of self-digestion involving the lysosomal degradation of cytoplasmic organelles and macromolecules. It occurs at low basal levels to perform housekeeping functions and is dramatically augmented upon nutrient depletion or exposure to other stresses, thus maintaining cellular homeostasis and energy balance and providing cytoprotective responses to adverse conditions. Mounting evidence that autophagy malfunction contributes to the pathogenesis of diverse human diseases has stimulated efforts to identify pharmacological agents that modulate autophagy in potentially beneficial ways. Here, we review the progresses accomplished toward this goal in recent years, as reflected by the patent literature.

Areas covered: Patent applications published from 2008 to mid-2012 that pertain to the pharmacological modulation of autophagy are reviewed and their potential therapeutic utilities are discussed.

Expert opinion: Of 40 patents related to autophagy, 21 claim novel enhancers or inhibitors of autophagy. One of the most promising applications of these compounds concerns cancer therapy, a few of them being already considered for clinical evaluation. Further work is, however, needed to identify compounds that target unique molecular effectors/regulators of autophagy to selectively modulate its various stages in different tissues and to design therapeutic interventions applicable to a broad variety of dysfunctional autophagy-associated disorders.

Keywords::

• AMPK
• autophagosome
• autophagy
• autophagy enhancer
• autophagy inhibitor
• Beclin-1
• cancer
• cell death
• cell survival
• mTORC1
• neurodegeneration
• ULK complex
• Vps34 complex

Acknowledgements

We thank Audrey Lindacher for her efficient librarian assistance. We also thank the anonymous referees for their helpful comments.

Notes

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