Poly(ADP-ribosyl)ation regulation of life and death in the nervous system

Research output: Contribution to journalReview articlepeer-review

Abstract

Poly(ADP-ribosyl)ation is required by multi-cellular eukaryotes to ensure genomic integrity under conditions of mild to moderate genotoxic stress. However, severe stress following acute neuronal injury causes over-activation of poly(ADP-ribose) polymerase-1, which results in unregulated poly(ADP-ribose) (PAR) synthesis and widespread neuronal cell death. Once thought to be a necrotic cell death resulting from energy failure, PARP-1 activation is now known to induce the nuclear translocation of apoptosis-inducing factor, which results in caspase-independent cell death. Conversely, poly(ADP-ribose) glycohydrolase, once thought to contribute to neuronal injury, now appears to have a protective role as demonstrated by recent studies utilizing gene disruption technology. Thus, the emerging mechanism dictating the fate of neurons appears to involve the regulation of PAR levels in neurons. Therefore, therapies targeting poly(ADP-ribosyl)ation in the treatment of neurodegenerative conditions such as stroke and Parkinson's disease are required to inhibit PAR synthesis and/or facilitate its degradation.

Original languageEnglish (US)
Pages (from-to)760-768
Number of pages9
JournalCellular and Molecular Life Sciences
Volume62
Issue number7-8
DOIs
StatePublished - Apr 1 2005

Keywords

  • Apoptosis
  • Apoptosis-inducing factor
  • Cell death
  • DNA damage
  • Excitotoxicity
  • PARG
  • PARP
  • Poly(ADP-ribose)

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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