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The key players of parthanatos: opportunities for targeting multiple levels in the therapy of parthanatos-based pathogenesis

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Abstract

Parthanatos is a form of regulated cell death involved in the pathogenesis of many diseases, particularly neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, Huntington’s disease, and amyotrophic lateral sclerosis. Parthanatos is a multistep cell death pathway cascade that involves poly (ADP-ribose) polymerase 1 (PARP-1) overactivation, PAR accumulation, PAR binding to apoptosis-inducing factor (AIF), AIF release from the mitochondria, nuclear translocation of the AIF/macrophage migration inhibitory factor (MIF) complex, and MIF-mediated large-scale DNA fragmentation. All the key players in the parthanatos pathway are pleiotropic proteins with diverse functions. An in-depth understanding of the structure-based activity of the key factors, and the biochemical mechanisms of parthanatos, is crucial for the development of drugs and therapeutic strategies. In this review, we delve into the key players of the parthanatos pathway and reveal the multiple levels of therapeutic opportunities for treating parthanatos-based pathogenesis.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (grant number: 31900557 to R.W., 31970686 to X.B. and 31801182 to Y.K.), China Postdoctoral Science Foundation Grant (grant number: 2019M662431 to R.W.).

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  1. Libo Liu and Jiaxiang Li have contributed equally to this work.

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  1. Institute of Biomedical Sciences, College of Life Sciences, Key Laboratory of Animal Resistance Biology of Shandong Provenice, Shandong Normal University, Jinan, 250014, Shandong, China

    Libo Liu, Jiaxiang Li, Jinmin Gao & Ruoxi Wang

  2. The Key Laboratory of Molecular Epigenetics of Education, School of Life Science, Northeast Normal University, Changchun, 130024, Jilin, China

    Yueshuang Ke, Xianlu Zeng & Xueqing Ba

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  1. Libo Liu
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RW and XB had the idea for the article; RW, LL and JL performed the literature search; RW, XB, LL, JL, JG, YK and XZ drafted and critically revised work; RW designed the figures. LL and RW produced the figures.

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Liu, L., Li, J., Ke, Y. et al. The key players of parthanatos: opportunities for targeting multiple levels in the therapy of parthanatos-based pathogenesis. Cell. Mol. Life Sci. 79, 60 (2022). https://doi.org/10.1007/s00018-021-04109-w

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