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

Seong-Woon Yu; Hongmin Wang; Ted M Dawson; Valina L Dawson

Neurobiology of Disease (Dec 2003)

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

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

Affiliations

Seong-Woon Yu: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Hongmin Wang: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Ted M Dawson: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Valina L Dawson: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA

Journal volume & issue: Vol. 14, no. 3
pp. 303 – 317

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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