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1.
Acta Pharmaceutica Sinica B ; (6): 4373-4390, 2023.
Artigo em Inglês | WPRIM | ID: wpr-1011188

RESUMO

Autophagy is a cellular process in which proteins and organelles are engulfed in autophagosomal vesicles and transported to the lysosome/vacuole for degradation. Protein-protein interactions (PPIs) play a crucial role at many stages of autophagy, which present formidable but attainable targets for autophagy regulation. Moreover, selective regulation of PPIs tends to have a lower risk in causing undesired off-target effects in the context of a complicated biological network. Thus, small-molecule regulators, including peptides and peptidomimetics, targeting the critical PPIs involved in autophagy provide a new opportunity for innovative drug discovery. This article provides general background knowledge of the critical PPIs involved in autophagy and reviews a range of successful attempts on discovering regulators targeting those PPIs. Successful strategies and existing limitations in this field are also discussed.

2.
Clinical Medicine of China ; (12): 466-470, 2022.
Artigo em Chinês | WPRIM | ID: wpr-956402

RESUMO

Autophagy is a highly conserved intracellular catabolic process used to degrade cytoplasmic components. In recent years, it has attracted much attention because of its importance in the pathogenesis and targeted therapy of acute and chronic kidney disease. Autophagy plays an important role in maintaining renal homeostasis under physiological and pathological conditions. The study of conditional autophagy related gene knockout specific to various renal cells has gradually revealed the role of autophagy in renal diseases. Recent studies have found that autophagy deficiency may play a key role in different pathological states of the kidney. Activated autophagy shows cytoprotective function in both glomerulus and renal tubulointerstitium, suggesting that the up regulation of autophagy may become a potential therapeutic strategy. However, there is also contrary evidence that autophagy may be harmful, which poses a great challenge to the development of therapeutic strategies for up-regulated autophagy.

3.
Journal of Shanghai Jiaotong University(Medical Science) ; (12): 1243-1247, 2019.
Artigo em Chinês | WPRIM | ID: wpr-843305

RESUMO

Objective • To study the effects of different phosphorylation levels of nuclear receptor-binding factor 2 (NRBF2) on the activity of class III phosphatidylinositol 3-kinase complex (PI3KC3-C1), and find a type of PI3KC3-C1 with the highest kinase activity as a target for the screening of autophagy-specific inhibitors. Methods • First, in vitro protein purification system was established to obtain quaternary NRBF2-free PI3KC3-C1 and quinary PI3KC3-C1 containing different phosphorylation levels of NRBF2. The integrity of the complex was determined by gel filtration chromatography. The different kinase activity of purified PI3KC3-C1 was detected in vitro, and thus the effect of phosphorylation of NRBF2 on PI3KC3-C1 activity was observed. Results • The purified PI3KC3-C1 had good purity and yield. The five-membered PI3KC3-C1 containing NRBF2 showed higher kinase activity than the quaternary protein complex, and PI3KC3-C1 containing the continuous dephosphorylated NBRF2 had the highest kinase activity. Conclusion • NRBF2 does exist as one of the components of PI3KC3-C1. The presence of NRBF2 promotes the kinase activity of PI3KC3-C1, and PI3KC3-C1 containing continuous dephosphorylation of NRBF2 may serve as a new regulatory target for the screening of autophagy-specific inhibitor.

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