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Activation of PARP by oxidative stress induced by β-amyloid: implications for Alzheimer's disease.
Neurochem Res. 2012 Nov; 37(11):2589-96.NR

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.

Authors+Show Affiliations

Department of Molecular Neuroscience, Institute of Neurology, UCL, Queen Square, London, WC1N 3BG, UK. r.abeti@ucl.ac.ukNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

23076628

Citation

Abeti, Rosella, and Michael R. Duchen. "Activation of PARP By Oxidative Stress Induced By Β-amyloid: Implications for Alzheimer's Disease." Neurochemical Research, vol. 37, no. 11, 2012, pp. 2589-96.
Abeti R, Duchen MR. Activation of PARP by oxidative stress induced by β-amyloid: implications for Alzheimer's disease. Neurochem Res. 2012;37(11):2589-96.
Abeti, R., & Duchen, M. R. (2012). Activation of PARP by oxidative stress induced by β-amyloid: implications for Alzheimer's disease. Neurochemical Research, 37(11), 2589-96. https://doi.org/10.1007/s11064-012-0895-x
Abeti R, Duchen MR. Activation of PARP By Oxidative Stress Induced By Β-amyloid: Implications for Alzheimer's Disease. Neurochem Res. 2012;37(11):2589-96. PubMed PMID: 23076628.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of PARP by oxidative stress induced by β-amyloid: implications for Alzheimer's disease. AU - Abeti,Rosella, AU - Duchen,Michael R, Y1 - 2012/10/18/ PY - 2012/04/06/received PY - 2012/09/21/accepted PY - 2012/09/21/revised PY - 2012/10/19/entrez PY - 2012/10/19/pubmed PY - 2013/4/24/medline SP - 2589 EP - 96 JF - Neurochemical research JO - Neurochem Res VL - 37 IS - 11 N2 - 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. SN - 1573-6903 UR - https://www.unboundmedicine.com/medline/citation/23076628/Activation_of_PARP_by_oxidative_stress_induced_by_β_amyloid:_implications_for_Alzheimer's_disease_ L2 - https://doi.org/10.1007/s11064-012-0895-x DB - PRIME DP - Unbound Medicine ER -