PARP-1 involvement in neurodegeneration: A focus on Alzheimer's and Parkinson's diseases

Mech Ageing Dev. 2015 Mar:146-148:53-64. doi: 10.1016/j.mad.2015.04.001. Epub 2015 Apr 13.

Abstract

DNA damage is the prime activator of the enzyme poly(ADP-ribose)polymerase1 (PARP-1) whose overactivation has been proven to be associated with the pathogenesis of numerous central nervous system disorders, such as ischemia, neuroinflammation, and neurodegenerative diseases. Under oxidative stress conditions PARP-1 activity increases, leading to an accumulation of ADP-ribose polymers and NAD(+) depletion, that induces energy crisis and finally cell death. This review aims to explain the contribution of PARP-1 in neurodegenerative diseases, focusing on Alzheimer's and Parkinson's disease, to stimulate further studies on this issue and thereby engage a new perspective regarding the design of possible therapeutic agents or the identification of biomarkers.

Keywords: Alzheimer’s disease; Mitochondria; Parkinson’s disease; Poly(ADP-ribose)polymerase.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Animals
  • Energy Metabolism*
  • Humans
  • Oxidative Stress*
  • Parkinson Disease / enzymology*
  • Parkinson Disease / genetics
  • Parkinson Disease / pathology
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism*

Substances

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