期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 13, 页码 -出版社
MDPI
DOI: 10.3390/ijms23137292
关键词
parthanatos; hallmarks; molecular mechanisms; related diseases
资金
- National Natural Science Foundation of China [81873226]
- Zhejiang Provincial Science and Technology Innovation Leading Talent Project of Ten Thousand Talents Plan (2019)
This article summarizes the hallmarks and molecular mechanisms of PARP1-mediated cell death (also known as parthanatos) and its role in various diseases. Excessive or defective parthanatos is critical in pathological cell damage, making further understanding of its mechanisms important for the treatment of related conditions.
Differential evolution of apoptosis, programmed necrosis, and autophagy, parthanatos is a form of cell death mediated by poly(ADP-ribose) polymerase 1 (PARP1), which is caused by DNA damage. PARP1 hyper-activation stimulates apoptosis-inducing factor (AIF) nucleus translocation, and accelerates nicotinamide adenine dinucleotide (NAD(+)) and adenosine triphosphate (ATP) depletion, leading to DNA fragmentation. The mechanisms of parthanatos mainly include DNA damage, PARP1 hyper-activation, PAR accumulation, NAD(+) and ATP depletion, and AIF nucleus translocation. Now, it is reported that parthanatos widely exists in different diseases (tumors, retinal diseases, neurological diseases, diabetes, renal diseases, cardiovascular diseases, ischemia-reperfusion injury...). Excessive or defective parthanatos contributes to pathological cell damage; therefore, parthanatos is critical in the therapy and prevention of many diseases. In this work, the hallmarks and molecular mechanisms of parthanatos and its related disorders are summarized. The questions raised by the recent findings are also presented. Further understanding of parthanatos will provide a new treatment option for associated conditions.
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