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聚(ADP - 核糖)聚合酶 -1及其在细胞生死过程中的模糊作用。

Poly(ADP-ribose) polymerase-1 and its ambiguous role in cellular life and death.

作者信息

Castedo Maria, Lafarge Antoine, Kroemer Guido

机构信息

Equipe 11 labellisée par la Ligue contre le Cancer, Université de Paris Cité, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, 75006 Paris, France.

Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.

出版信息

Cell Stress. 2023 Jan 23;7(1):1-6. doi: 10.15698/cst2023.01.275. eCollection 2023 Jan.

Abstract

The deletion of the gene coding for poly(ADP-ribose) polymerase-1 (PARP1) or its pharmacological inhibition protects mice against cerebral ischemia and Parkinson's disease. In sharp contrast, PARP1 inhibitors are in clinical use for the eradication of vulnerable cancer cells. It appears that excessive PARP1 activation is involved in a specific cell death pathway called parthanatos, while inhibition of PARP1 in cancer cells amplifies DNA damage to a lethal level. Hence, PARP1 plays a context-dependent role in cell fate decisions. In addition, it appears that PARP1 plays an ambiguous role in organismal aging.

摘要

编码聚(ADP - 核糖)聚合酶 -1(PARP1)的基因缺失或其药理学抑制可保护小鼠免受脑缺血和帕金森病的影响。与之形成鲜明对比的是,PARP1抑制剂正在临床上用于根除易损癌细胞。似乎过度的PARP1激活参与了一种称为parthanatos的特定细胞死亡途径,而癌细胞中PARP1的抑制会将DNA损伤放大到致死水平。因此,PARP1在细胞命运决定中发挥着依赖于上下文的作用。此外,PARP1似乎在生物体衰老中也起着模糊的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d77f/9877585/7bc7c2c56853/ces-07-001-g001.jpg

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