Poly(ADP-ribose) polymerase-1 and apoptosis inducing factor in neurotoxicity

Seong Woon Yu, Hongmin Wang, Ted M. Dawson, Valina L. Dawson

Research output: Contribution to journalReview articlepeer-review

169 Scopus citations


Poly(ADP-ribose) polymerase-1 (PARP-1) is the guardian of the genome acting as a sentinel for genomic damage. However, PARP-1 is also mediator of cell death after ischemia-reperfusion injury, glutamate excitotoxicity, and various inflammatory processes. The biochemistry underlying PARP-1-mediated cell death has remained elusive, although NAD+ consumption and energy failure have been thought to be one of the possible molecular mechanisms. Recent observations link PARP-1 activation with translocation of apoptosis-inducing factor (AIF) to the nucleus and indicate that AIF is an essential downstream effector of PARP-1-mediated cell death. PARP-1 activation signals AIF release from the mitochondria, resulting in a novel, caspase-independent pathway of programmed cell death. These recent findings suggest that AIF maybe a target for development of future therapeutic treatment for many neurological disorders involving excitotoxicity.

Original languageEnglish (US)
Pages (from-to)303-317
Number of pages15
JournalNeurobiology of Disease
Issue number3
StatePublished - Dec 2003

ASJC Scopus subject areas

  • Neurology


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