Application and interpretation of current autophagy inhibitors and activators - PubMed (original) (raw)

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Application and interpretation of current autophagy inhibitors and activators

Ya-ping Yang et al. Acta Pharmacol Sin. 2013 May.

Abstract

Autophagy is the major intracellular degradation system, by which cytoplasmic materials are delivered to and degraded in the lysosome. As a quality control mechanism for cytoplasmic proteins and organelles, autophagy plays important roles in a variety of human diseases, including neurodegenerative diseases, cancer, cardiovascular disease, diabetes and infectious and inflammatory diseases. The discovery of ATG genes and the dissection of the signaling pathways involved in regulating autophagy have greatly enriched our knowledge on the occurrence and development of this lysosomal degradation pathway. In addition to its role in degradation, autophagy may also promote a type of programmed cell death that is different from apoptosis, termed type II programmed cell death. Owing to the dual roles of autophagy in cell death and the specificity of diseases, the exact mechanisms of autophagy in various diseases require more investigation. The application of autophagy inhibitors and activators will help us understand the regulation of autophagy in human diseases, and provide insight into the use of autophagy-targeted drugs. In this review, we summarize the latest research on autophagy inhibitors and activators and discuss the possibility of their application in human disease therapy.

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Figure 1

Figure 1

Pharmacological targeting of control points in the autophagic pathway. EBSS, Earle's Balanced Salt Solution; ER, endoplasmic reticulum; mTOR, mammalian target of rapamycin; PI3K, phosphatidylinositol 3-kinase; SMER, small molecule enhancers of rapamycin; IMPase, inositol monophosphatase; IP3R, inositol-1,4,5-triphosphate receptor; HDAC6, histone deacetylase 6; 3-MA, 3-methyladenine; ATG, autophagy-specific gene.

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