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Activation of PARP by Oxidative Stress Induced by β-Amyloid: Implications for Alzheimer’s Disease


Alzheimer’s disease (AD) is a major neurodegenerative disease of old age, characterised by progressive cognitive impairment, dementia and atrophy of the central nervous system. The pathological hallmarks include the accumulation of the peptide β-amyloid (Aβ) which itself is toxic to neurons in culture. Recently, it has been discovered that Aβ activates the protein poly(ADP-ribosyl) polymerase-1 (PARP-1) specifically in astrocytes, leading indirectly to neuronal cell death. PARP-1 is a DNA repair enzyme, normally activated by single strand breaks associated with oxidative stress, which catalyses the formation of poly ADP-ribose polymers from nicotinamide adenine dinucleotide (NAD+). The pathological over activation of PARP-1 causes depletion of NAD+ and leads to cell death. Here we review the relationship between AD and PARP-1, and explore the role played by astrocytes in neuronal death. AD has so far proven refractory to any effective treatment. Identification of these pathways represents a step towards a greater understanding of the pathophysiology of this devastating disease with the potential to explore novel therapeutic targets.

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Correspondence to Rosella Abeti.

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Special Issue: In Honor of Leif Hertz.

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Abeti, R., Duchen, M.R. Activation of PARP by Oxidative Stress Induced by β-Amyloid: Implications for Alzheimer’s Disease. Neurochem Res 37, 2589–2596 (2012).

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  • Alzheimer’s disease
  • β-amyloid
  • PARP-1
  • Astrocytes
  • Oxidative stress and mitochondria