Poly (ADP-ribose) (PAR)-dependent cell death in neurodegenerative diseases

Hyejin Park; Tae-In Kam; Ted M Dawson; Valina L Dawson

doi:10.1016/bs.ircmb.2019.12.009

Poly (ADP-ribose) (PAR)-dependent cell death in neurodegenerative diseases

Int Rev Cell Mol Biol. 2020:353:1-29. doi: 10.1016/bs.ircmb.2019.12.009. Epub 2020 Jan 27.

Authors

Hyejin Park¹, Tae-In Kam¹, Ted M Dawson², Valina L Dawson³

Affiliations

¹ Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
² Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, United States; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States. Electronic address: tdawson@jhmi.edu.
³ Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, United States; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States. Electronic address: vdawson1@jhmi.edu.

PMID: 32381174
DOI: 10.1016/bs.ircmb.2019.12.009

Abstract

Disruption of cellular functions with aging-induced accumulation of neuronal stressors causes cell death which is a common feature of neurodegenerative diseases. Studies in a variety of neurodegenerative disease models demonstrate that poly (ADP-ribose) (PAR)-dependent cell death, also named parthanatos, is responsible for neuronal loss in neurological diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Parthanatos has distinct features that differ from caspase-dependent apoptosis, necrosis or autophagic cell death. Parthanatos can be triggered by the accumulation of PAR due to overactivation of PAR polymerase-1 (PARP-1). Excess PAR, induces the mitochondrial release apoptosis-inducing factor (AIF), which binds to macrophage migration inhibitory factor (MIF) carrying MIF into the nucleus where it cleaves genomic DNA into large fragments. In this review, we will discuss the molecular mechanisms of parthanatos and their role in neurodegenerative diseases. Furthermore, we will discuss promising therapeutic interventions within the pathological PAR signaling cascade that could be designed to halt the progression of neurodegeneration.

Keywords: AIF; Cell death; MIF; Neurodegenerative disease; PAR; PARP-1; Parthanatos; Poly (ADP-ribose).

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Cell Death*
Humans
Neurodegenerative Diseases / metabolism*
Neurodegenerative Diseases / pathology
Poly Adenosine Diphosphate Ribose / metabolism*

Substances

Poly Adenosine Diphosphate Ribose