The role of PARP1 in neurodegenerative diseases and aging

FEBS J. 2022 Apr;289(8):2013-2024. doi: 10.1111/febs.15716. Epub 2021 Feb 8.

Abstract

Neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by progressive memory loss and motor impairment. Aging is a major risk factor for neurodegenerative diseases. Neurodegenerative diseases and aging often develop in an irreversible manner and cause a significant socioeconomic burden. When considering their pathogenesis, many studies usually focus on mitochondrial dysfunction and DNA damage. More recently, neuroinflammation, autophagy dysregulation, and SIRT1 inactivation were shown to be involved in the pathogenesis of neurodegenerative diseases and aging. In addition, studies uncovered the role of poly (ADP-ribose)-polymerase-1 (PARP1) in neurodegenerative diseases and aging. PARP1 links to a cluster of stress signals, including those originated by inflammation and autophagy dysregulation. In this review, we summarized the recent research progresses on PARP1 in neurodegenerative diseases and aging, with an emphasis on the relationship among PARP1, neuroinflammation, mitochondria, and autophagy. We discussed the possibilities of treating neurodegenerative diseases and aging through targeting PARP1.

Keywords: DNA damage; PARP1; aging; neurodegenerative diseases; neuroinflammation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Autophagy / genetics
  • Humans
  • Mitochondria / genetics
  • Neurodegenerative Diseases* / genetics
  • Poly (ADP-Ribose) Polymerase-1 / genetics
  • Sirtuin 1

Substances

  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Sirtuin 1