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Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles
Open accessAbstract
Autophagy is central to the maintenance of organismal homeostasis in both physiological and pathological situations. Accordingly, alterations in autophagy have been linked to clinically relevant conditions as diverse as cancer, neurodegeneration and cardiac disorders. Throughout the past decade, autophagy has attracted considerable attention as a target for the development of novel therapeutics. However, such efforts have not yet generated clinically viable interventions. In this Review, we discuss the therapeutic potential of autophagy modulators, analyse the obstacles that have limited their development and propose strategies that may unlock the full therapeutic potential of autophagy modulation in the clinic.
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“and permanent or transient endogenous defects in autophagy have been associated with embryonic lethality, developmental defects, and multiple pathological disorders, including (but not limited to) neurodegeneration, cancer, and cardiovascular disorders [812–817].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [815]
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“mTOR inhibitors, such as rapamycin, rapamycin analogues and mTORC1 kinase inhibitors, are already widely used as immunosuppressive agents in clinical settings18.”
From Autophagy in kidney homeostasis and disease (2020) · cites this paper as [18]
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“The expanding list of chemical activators of autophagy includes mTOR inhibitors and mTOR-independent agents18,29,36,192.”
From Autophagy in kidney homeostasis and disease (2020) · cites this paper as [18]
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Metadata
- Authors
- Galluzzi, L., Bravo-San Pedro, J. M., Levine, B., Green, D. R., & Kroemer, G.
- Affiliations
- Sorbonne Paris Cité (FR)
- Howard Hughes Medical Institute (US)
- St. Jude Children's Research Hospital (US)
- Karolinska University Hospital (SE)
- Corresponding author
- Galluzzi, Lorenzo
- Venue
- Nature Reviews Drug Discovery
- Published
- 2017-05-19
- Volume
- 16
- Issue
- 7
- Pages
- 487-511
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- PMC
- PMC5713640
- OpenAlex
- W2615994102
- Cited by
- 842
- References
- 307
- Citations by year
- 2026: 47 · 2025: 63 · 2024: 90 · 2023: 90 · 2022: 103 · 2021: 93 · 2020: 118 · 2019: 113 · 2018: 95 · 2017: 30
- FWCI
- 12.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (cc-by)
- Funders
- National Cancer Institute (R01CA109618)
- National Institute of Allergy and Infectious Diseases (U19AI109725)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- autophagy, autophagy modulators, drug development, cancer, neurodegenerative diseases, cardiovascular disease, infectious diseases, homeostasis, therapeutic target
- MeSH terms
- Animals, Autophagy, Heart Diseases, Humans, Neoplasms, Drug Design, Neurodegenerative Diseases, Molecular Targeted Therapy
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