Poly(ADP-ribose) polymerase-1 and apoptosis inducing factor in neurotoxicity.
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.
Yu
Seong-Woon
SW
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Wang
Hongmin
H
Dawson
Ted M
TM
Dawson
Valina L
VL
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009410:Nerve Degeneration / Q000201:enzymology* / Q000503:physiopathology; D009420:Nervous System / Q000201:enzymology* / Q000503:physiopathology; D009498:Neurotoxins / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; D009498:Neurotoxins; D011065:Poly(ADP-ribose) Polymerases