title: 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.
authors.affiliation: Institut Necker-Enfants Malades (INEM), INSERM U1151-CNRS UMR 8253, F-75993 Paris, France; email: patrice.codogno@inserm.fr.|Université Paris Descartes-Sorbonne Paris Cité, F-75012 Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Morel
authors.affiliation: Institut Necker-Enfants Malades (INEM), INSERM U1151-CNRS UMR 8253, F-75993 Paris, France; email: patrice.codogno@inserm.fr.|Université Paris Descartes-Sorbonne Paris Cité, F-75012 Paris, France.
authors.forename: Maryam
authors.initials: M
authors.lastname: Mehrpour
authors.affiliation: Institut Necker-Enfants Malades (INEM), INSERM U1151-CNRS UMR 8253, F-75993 Paris, France; email: patrice.codogno@inserm.fr.|Université Paris Diderot-Sorbonne Paris Cité, F-75993 Paris, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Botti
authors.affiliation: Institut Necker-Enfants Malades (INEM), INSERM U1151-CNRS UMR 8253, F-75993 Paris, France; email: patrice.codogno@inserm.fr.|Université Paris Descartes-Sorbonne Paris Cité, F-75012 Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupont
authors.affiliation: Institut Necker-Enfants Malades (INEM), INSERM U1151-CNRS UMR 8253, F-75993 Paris, France; email: patrice.codogno@inserm.fr.|Université Paris Descartes-Sorbonne Paris Cité, F-75012 Paris, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hamaï
authors.affiliation: Institut Necker-Enfants Malades (INEM), INSERM U1151-CNRS UMR 8253, F-75993 Paris, France; email: patrice.codogno@inserm.fr.|Université Paris Descartes-Sorbonne Paris Cité, F-75012 Paris, France.
authors.forename: Anna Chiara
authors.initials: AC
authors.lastname: Nascimbeni
authors.affiliation: Institut Necker-Enfants Malades (INEM), INSERM U1151-CNRS UMR 8253, F-75993 Paris, France; email: patrice.codogno@inserm.fr.|Université Paris Descartes-Sorbonne Paris Cité, F-75012 Paris, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Codogno
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002986:Clinical Trials as Topic / Q000379:methods; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D020123:Sirolimus
keywords: activators; autophagosome; disease; inhibitors; lysosome; macroautophagy