Journal
MEDICINAL RESEARCH REVIEWS
Volume 42, Issue 6, Pages 2067-2101Publisher
WILEY
DOI: 10.1002/med.21917
Keywords
apoptosis; ischemia; reperfusion; mitochondria; regulated cell death; small molecule
Categories
Funding
- National Natural Science Foundation of China [82104511]
- Postdoctoral Science Foundation of China [2021M693579]
- Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine [ZYYCXTD-C-202005]
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Ischemia/reperfusion (IR) injury is a major contributor to disability and mortality worldwide. Few interventions specifically targeting the pathogenesis of IR injury are available. Recent advances suggest that small molecules targeting regulated cell death pathways may provide beneficial effects against IR injury.
Ischemia/reperfusion (IR) injury contributes to disability and mortality worldwide. Due to the complicated mechanisms and lack of proper therapeutic targets, few interventions are available that specifically target the pathogenesis of IR injury. Regulated cell death (RCD) of endothelial and parenchymal cells is recognized as the promising intervening target. Recent advances in IR injury suggest that small molecules exhibit beneficial effects on various RCD against IR injury, including apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis, and parthanatos. Here, we describe the mechanisms behind these novel promising therapeutic targets and explain the machinery powering the small molecules. These small molecules exert protection by targeting endothelial or parenchymal cells to alleviate IR injury. Therapies of the ideal combination of small molecules targeting multiple cell types have shown potent synergetic therapeutic effects, laying the foundation for novel strategies to attenuate IR injury.
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