Autophagy: A Druggable Process
- PMID: 28061686
- DOI: 10.1146/annurev-pharmtox-010716-104936
Autophagy: A Druggable Process
Abstract
Macroautophagy (hereafter called autophagy) is a vacuolar, lysosomal pathway for catabolism of intracellular material that is conserved among eukaryotic cells. Autophagy plays a crucial role in tissue homeostasis, adaptation to stress situations, immune responses, and the regulation of the inflammatory response. Blockade or uncontrolled activation of autophagy is associated with cancer, diabetes, obesity, cardiovascular disease, neurodegenerative disease, autoimmune disease, infection, and chronic inflammatory disease. During the past decade, researchers have made major progress in understanding the three levels of regulation of autophagy in mammalian cells: signaling, autophagosome formation, and autophagosome maturation and lysosomal degradation. As we discuss in this review, each of these levels is potentially druggable, and, depending on the indication, may be able to stimulate or inhibit autophagy. We also summarize the different modulators of autophagy and their potential and limitations in the treatment of life-threatening diseases.
Keywords: activators; autophagosome; disease; inhibitors; lysosome; macroautophagy.
Similar articles
-
Targeting autophagy using natural compounds for cancer prevention and therapy.Cancer. 2019 Apr 15;125(8):1228-1246. doi: 10.1002/cncr.31978. Epub 2019 Feb 12. Cancer. 2019. PMID: 30748003 Review.
-
Fine-tuning autophagy: from transcriptional to posttranslational regulation.Am J Physiol Cell Physiol. 2016 Sep 1;311(3):C351-62. doi: 10.1152/ajpcell.00129.2016. Epub 2016 Jun 22. Am J Physiol Cell Physiol. 2016. PMID: 27335173 Review.
-
Recent advances in autophagy-based neuroprotection.Expert Rev Neurother. 2015 Feb;15(2):195-205. doi: 10.1586/14737175.2015.1002087. Expert Rev Neurother. 2015. PMID: 25614954 Review.
-
Autophagy: A protective mechanism in response to stress and inflammation.Curr Opin Investig Drugs. 2006 May;7(5):443-50. Curr Opin Investig Drugs. 2006. PMID: 16729721 Free PMC article. Review.
-
Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities.Neuron. 2017 Mar 8;93(5):1015-1034. doi: 10.1016/j.neuron.2017.01.022. Neuron. 2017. PMID: 28279350 Review.
Cited by
-
The role of autophagy and ferroptosis in sensorineural hearing loss.Front Neurosci. 2022 Dec 12;16:1068611. doi: 10.3389/fnins.2022.1068611. eCollection 2022. Front Neurosci. 2022. PMID: 36578828 Free PMC article. Review.
-
Stress-induced tunneling nanotubes support treatment adaptation in prostate cancer.Sci Rep. 2019 May 24;9(1):7826. doi: 10.1038/s41598-019-44346-5. Sci Rep. 2019. PMID: 31127190 Free PMC article.
-
Autophagy Stimulus Promotes Early HuR Protein Activation and p62/SQSTM1 Protein Synthesis in ARPE-19 Cells by Triggering Erk1/2, p38MAPK, and JNK Kinase Pathways.Oxid Med Cell Longev. 2018 Feb 8;2018:4956080. doi: 10.1155/2018/4956080. eCollection 2018. Oxid Med Cell Longev. 2018. PMID: 29576851 Free PMC article.
-
Overexpression of lncRNA SLC26A4-AS1 inhibits papillary thyroid carcinoma progression through recruiting ETS1 to promote ITPR1-mediated autophagy.J Cell Mol Med. 2021 Sep;25(17):8148-8158. doi: 10.1111/jcmm.16545. Epub 2021 Aug 10. J Cell Mol Med. 2021. PMID: 34378314 Free PMC article.
-
Small Trafficking Inhibitor Retro-2 Disrupts the Microtubule-Dependent Trafficking of Autophagic Vacuoles.Front Cell Dev Biol. 2020 Jun 18;8:464. doi: 10.3389/fcell.2020.00464. eCollection 2020. Front Cell Dev Biol. 2020. PMID: 32626708 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous