Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles

By L. Galluzzi, J. M. Bravo-San Pedro, Beth Levine, Douglas R. Green, Guido Kroemer. Nature reviews. Drug discovery, 2017

772 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Pharmacology, Physiology

View Paper: https://www.semanticscholar.org/paper/8ae0546057c81a0664565651ffb5cd878a54b2bf

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. L. Galluzzi
2. Guido Kroemer
3. Douglas R. Green
4. F. Reggiori
5. Beth Levine
6. V. Deretic
7. Guillermo Mariño
8. N. Mizushima

In Pharmacology

1. L. Galluzzi
2. Douglas R. Green
3. Guido Kroemer
4. Beth Levine

In Physiology

1. L. Galluzzi
2. Guido Kroemer
3. F. Reggiori
4. Douglas R. Green
5. V. Schirrmacher

Citations in the corpus

• Mitochondrial metabolism and cancer (2017, background): “That said, slightly elevated ROS levels may increase the resistance of cancer cells to RCD by (1) triggering an adaptative hormetic response reminiscent of ischemic preconditioning [108, 109], and/or (2) promoting autophagy activation [110].”
• Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion (2018, background): “Inhibition of autophagy in particular, appears to be beneficial to treat specific types of tumors, chronic obstructive pulmonary diseases, neonatal asphyxia and defined inflammatory diseases [17].”
• Autophagy-Independent Functions of the Autophagy Machinery (2019, background): “In particular, this may have led investigators to misattribute phenotypic or functional effects caused by the pharmacological or genetic perturbation of single autophagy-regulatory factors to autophagy as a process (Galluzzi et al., 2017b) .”
• Molecular definitions of autophagy and related processes (2017, neutral): “…all, pharmacological agents employed so far for suppressing macroautophagic responses (Maycotte et al , 2012; Maes et al , 2014; Eng et al , 2016; Galluzzi et al , 2017b); and (ii) multiple components of the macroautophagy machinery have autophagy-independent functions (Hwang et al , 2012;…”