Autophagy modulation as a potential therapeutic target for diverse diseases

By D. Rubinsztein, P. Codogno, Beth Levine. Nature reviews. Drug discovery, 2012

1,424 citations recorded by the source corpus.

Autophagy is an essential, conserved lysosomal degradation pathway that controls the quality of the cytoplasm by eliminating protein aggregates and damaged organelles. It begins when double-membraned autophagosomes engulf portions of the cytoplasm, which is followed by fusion of these vesicles with lysosomes and degradation of the autophagic contents. In addition to its vital homeostatic role, this degradation pathway is involved in various human disorders, including metabolic conditions, neurodegenerative diseases, cancers and infectious diseases. This article provides an overview of the mechanisms and regulation of autophagy, the role of this pathway in disease and strategies for therapeutic modulation.

Subfields: Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/d664d4c4d4df50c41fe75213ab6cf02437913c3c

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Citations in the corpus

mTOR: a pharmacologic target for autophagy regulation. (2015, neutral): “81, 82).”
Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities. (2017, positive): “Furthermore, most aggregate-prone, neurodegenerative disease-associated proteins have been shown to be autophagy substrates, including mutant huntingtin, alpha-synuclein, and tau (Berger et al., 2006; Ravikumar et al., 2002; Ravikumar et al., 2004; Webb et al., 2003); (Rubinsztein et al., 2012).”
An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma (2016, positive): “We also noted increases in a large number of dipeptides (Figure 3A) that may be produced through protein degradation/reutilization processes, such as lysosomal degradation, phagocytosis, endocytosis, pinocytosis, and autophagy (Commisso et al., 2013; Kimmelman, 2015; Mizushima and Komatsu, 2011; Rub”
Autophagy in malignant transformation and cancer progression (2015, positive): “…and hydroxychloroquine (HCQ), two lysosomo-tropic drugs approved by the US Food and Drug Administration for the prophylactic treatment of malaria and for the management of (chronic, discoid or systemic) lupus erythematosus as well as acute or chronic rheumatoid arthritis (Rubinsztein et al , 2012).”
Emerging functions of the EGFR in cancer (2017, background): “…in different pathologies, including neurodegenerative diseases, aging, and cancer, and is one of the major mechanisms promoting resistance to cancer therapies (for recent reviews see, for instance Galluzzi et al., 2015, 2017; Goldsmith et al., 2014; Menzies et al., 2015; Rubinsztein et al., 2012).”
Emerging regulation and functions of autophagy (2013, background): “Several signalling molecules and cascades modulate autophagy in response to numerous cellular and environmental cues 25, 26 .”
Lysosomes as a therapeutic target (2019, background): “This phe nomenon makes it highly challenging to identify a single drug able to correct a failure, unless a cell specific target ing molecule could be incorporated into the autophagy activator/inhibitor to enable tissue specificity 205 .”