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Chemical modulators of autophagy as biological probes and potential therapeutics

Abstract

Autophagy is an evolutionarily conserved mechanism for protein degradation that is critical for the maintenance of homeostasis in man. Autophagy has unexpected pleiotropic functions that favor survival of the cell, including nutrient supply under starvation, cleaning of the cellular interior, defense against infection and antigen presentation. Moreover, defective autophagy is associated with a diverse range of disease states, including neurodegeneration, cancer and Crohn's disease. Here we discuss the roles of mammalian autophagy in health and disease and highlight recent advances in pharmacological manipulation of autophagic pathways as a therapeutic strategy for a variety of pathological conditions.

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Figure 1: Schematic of autophagy.
Figure 2: Schematic representation of the mTOR signaling pathway.
Figure 3: mTOR-independent autophagy induction pathways.

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Acknowledgements

We are grateful for funding from the Medical Research Council (Programme Grant to D.C.R.; Skills Gap Award to A.F.), the Wellcome Trust (Senior Fellowship to D.C.R.), the UK National Institute for Health Research, Biomedical Research Centre at Addenbrooke's Hospital, Special Coordination Funds for Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Takeda Science Foundation.

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Correspondence to Tamotsu Yoshimori or David C Rubinsztein.

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David Rubinsztein is an inventor on patents describing autophagy-inducing drugs as potential therapeutics.

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Fleming, A., Noda, T., Yoshimori, T. et al. Chemical modulators of autophagy as biological probes and potential therapeutics. Nat Chem Biol 7, 9–17 (2011). https://doi.org/10.1038/nchembio.500

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