4.7 Review

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

Journal

CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 79, Issue 1, Pages -

Publisher

SPRINGER BASEL AG
DOI: 10.1007/s00018-021-04109-w

Keywords

Cell death; PARP1; AIF; MIF; Neurodegenerative diseases; Therapeutic target

Funding

  1. National Natural Science Foundation of China [31900557, 31970686, 31801182]
  2. China Postdoctoral Science Foundation [2019M662431]

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Parthanatos is a form of regulated cell death that plays a role in the pathogenesis of many diseases, particularly neurodegenerative disorders. Understanding the key factors and biochemical mechanisms of the Parthanatos pathway is essential for developing drugs and therapeutic strategies.
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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