Neurochemical Research

, Volume 37, Issue 11, pp 2589–2596

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

Overview

DOI: 10.1007/s11064-012-0895-x

Cite this article as:
Abeti, R. & Duchen, M.R. Neurochem Res (2012) 37: 2589. doi:10.1007/s11064-012-0895-x

Abstract

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.

Keywords

Alzheimer’s diseaseβ-amyloidPARP-1AstrocytesOxidative stress and mitochondria

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Department of Molecular NeuroscienceInstitute of Neurology, UCLLondonUK
  2. 2.Department of Cell and Developmental BiologyUniversity College LondonLondonUK