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PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage

Amyloid beta peptide (Aβ) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma ce...

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Autores principales: Martire, Sara, Fuso, Andrea, Rotili, Dante, Tempera, Italo, Giordano, Cesare, De Zottis, Ivana, Muzi, Alessia, Vernole, Patrizia, Graziani, Grazia, Lococo, Emanuela, Faraldi, Martina, Maras, Bruno, Scarpa, Sigfrido, Mosca, Luciana, d'Erme, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782458/
https://www.ncbi.nlm.nih.gov/pubmed/24086258
http://dx.doi.org/10.1371/journal.pone.0072169
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author Martire, Sara
Fuso, Andrea
Rotili, Dante
Tempera, Italo
Giordano, Cesare
De Zottis, Ivana
Muzi, Alessia
Vernole, Patrizia
Graziani, Grazia
Lococo, Emanuela
Faraldi, Martina
Maras, Bruno
Scarpa, Sigfrido
Mosca, Luciana
d'Erme, Maria
author_facet Martire, Sara
Fuso, Andrea
Rotili, Dante
Tempera, Italo
Giordano, Cesare
De Zottis, Ivana
Muzi, Alessia
Vernole, Patrizia
Graziani, Grazia
Lococo, Emanuela
Faraldi, Martina
Maras, Bruno
Scarpa, Sigfrido
Mosca, Luciana
d'Erme, Maria
author_sort Martire, Sara
collection PubMed
description Amyloid beta peptide (Aβ) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with Aβ(25–35) fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. Aβ(25–35) induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following Aβ(25–35) exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that Aβ(25–35) induces DNA damage which in turn activates PARP-1. Challenge with Aβ(25–35) is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, Aβ(25–35) via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by Aβ and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed.
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spelling pubmed-37824582013-10-01 PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage Martire, Sara Fuso, Andrea Rotili, Dante Tempera, Italo Giordano, Cesare De Zottis, Ivana Muzi, Alessia Vernole, Patrizia Graziani, Grazia Lococo, Emanuela Faraldi, Martina Maras, Bruno Scarpa, Sigfrido Mosca, Luciana d'Erme, Maria PLoS One Research Article Amyloid beta peptide (Aβ) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with Aβ(25–35) fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. Aβ(25–35) induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following Aβ(25–35) exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that Aβ(25–35) induces DNA damage which in turn activates PARP-1. Challenge with Aβ(25–35) is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, Aβ(25–35) via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by Aβ and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed. Public Library of Science 2013-09-24 /pmc/articles/PMC3782458/ /pubmed/24086258 http://dx.doi.org/10.1371/journal.pone.0072169 Text en © 2013 Martire et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Martire, Sara
Fuso, Andrea
Rotili, Dante
Tempera, Italo
Giordano, Cesare
De Zottis, Ivana
Muzi, Alessia
Vernole, Patrizia
Graziani, Grazia
Lococo, Emanuela
Faraldi, Martina
Maras, Bruno
Scarpa, Sigfrido
Mosca, Luciana
d'Erme, Maria
PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage
title PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage
title_full PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage
title_fullStr PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage
title_full_unstemmed PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage
title_short PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage
title_sort parp-1 modulates amyloid beta peptide-induced neuronal damage
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782458/
https://www.ncbi.nlm.nih.gov/pubmed/24086258
http://dx.doi.org/10.1371/journal.pone.0072169
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