Alzheimer's disease-associated neurotoxic peptide amyloid-beta impairs base excision repair in human neuroblastoma cells (525 views)
Int J Mol Sc (ISSN: 1422-0067linking, 1422-0067electronic, 1661-6596), 2012 Nov 13; 13(11): 14766-14787.
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Paper type: Journal Article, Research Support, Non-U. S. Gov'T,
Impact factor: 2.464, 5-year impact factor: 2.732
Url: Not available.
Keywords: Alzheimer Disease Metabolism, Amyloid Beta-Peptides Genetics Metabolism, Cell Line, Tumor, Dna Damage Drug Effects Genetics, Dna Repair Drug Effects Genetics, Mitochondrial Genetics Metabolism, Gene Expression, Gene Expression Regulation, Neoplastic, Guanosine Analogs, Derivatives Metabolism, Humans, Neuroblastoma Genetics Metabolism, Oxidants Pharmacology, Oxidative Stress Drug Effects Genetics, Peptide Fragments Genetics Metabolism,
Affiliations:
*** IBB - CNR ***
Nucleic Acids Lesions Laboratory, SCIB/INAC, CEA, Joseph Fourier University-Grenoble 1, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France. walid.rachidi@cea.fr.
References:
Not available.
Int J Mol Sc (ISSN: 1422-0067linking, 1422-0067electronic, 1661-6596), 2012 Nov 13; 13(11): 14766-14787.
Export to BibTeX Export to EndNote
Paper type: Journal Article, Research Support, Non-U. S. Gov'T,
Impact factor: 2.464, 5-year impact factor: 2.732
Url: Not available.
Keywords: Alzheimer Disease Metabolism, Amyloid Beta-Peptides Genetics Metabolism, Cell Line, Tumor, Dna Damage Drug Effects Genetics, Dna Repair Drug Effects Genetics, Mitochondrial Genetics Metabolism, Gene Expression, Gene Expression Regulation, Neoplastic, Guanosine Analogs, Derivatives Metabolism, Humans, Neuroblastoma Genetics Metabolism, Oxidants Pharmacology, Oxidative Stress Drug Effects Genetics, Peptide Fragments Genetics Metabolism,
Affiliations:
*** IBB - CNR ***
Nucleic Acids Lesions Laboratory, SCIB/INAC, CEA, Joseph Fourier University-Grenoble 1, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France. walid.rachidi@cea.fr.
References:
Not available.
Alzheimer's disease-associated neurotoxic peptide amyloid-beta impairs base excision repair in human neuroblastoma cells
Alzheimer's disease (AD) is the leading cause of dementia in developed countries. It is characterized by two major pathological hallmarks, one of which is the extracellular aggregation of the neurotoxic peptide amyloid-beta (Abeta), which is known to generate oxidative stress. In this study, we showed that the presence of Abeta in a neuroblastoma cell line led to an increase in both nuclear and mitochondrial DNA damage. Unexpectedly, a concomitant decrease in basal level of base excision repair, a major route for repairing oxidative DNA damage, was observed at the levels of both gene expression and protein activity. Moreover, the addition of copper sulfate or hydrogen peroxide, used to mimic the oxidative stress observed in AD-affected brains, potentiates Abeta-mediated perturbation of DNA damage/repair systems in the "Abeta cell line". Taken together, these findings indicate that Abeta could act as double-edged sword by both increasing oxidative nuclear/mitochondrial damage and preventing its repair. The synergistic effects of increased ROS production, accumulated DNA damage and impaired DNA repair could participate in, and partly explain, the massive loss of neurons observed in Alzheimer's disease since both oxidative stress and DNA damage can trigger apoptosis.
Alzheimer's disease (AD) is the leading cause of dementia in developed countries. It is characterized by two major pathological hallmarks, one of which is the extracellular aggregation of the neurotoxic peptide amyloid-beta (Abeta), which is known to generate oxidative stress. In this study, we showed that the presence of Abeta in a neuroblastoma cell line led to an increase in both nuclear and mitochondrial DNA damage. Unexpectedly, a concomitant decrease in basal level of base excision repair, a major route for repairing oxidative DNA damage, was observed at the levels of both gene expression and protein activity. Moreover, the addition of copper sulfate or hydrogen peroxide, used to mimic the oxidative stress observed in AD-affected brains, potentiates Abeta-mediated perturbation of DNA damage/repair systems in the "Abeta cell line". Taken together, these findings indicate that Abeta could act as double-edged sword by both increasing oxidative nuclear/mitochondrial damage and preventing its repair. The synergistic effects of increased ROS production, accumulated DNA damage and impaired DNA repair could participate in, and partly explain, the massive loss of neurons observed in Alzheimer's disease since both oxidative stress and DNA damage can trigger apoptosis.
Alzheimer's disease-associated neurotoxic peptide amyloid-beta impairs base excision repair in human neuroblastoma cells
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Alzheimer's disease-associated neurotoxic peptide amyloid-beta impairs base excision repair in human neuroblastoma cells
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Giuffrida ML, Tomasello F, Caraci F, Chiechio S, Nicoletti F, Copani A
* Beta-Amyloid monomer and insulin/IGF-1 signaling in Alzheimer's disease (1943 views)
Mol Neurobiol (ISSN: 0893-7648), 2012 Dec; 46(3): 605-613.
Impact Factor: 5.471
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Grasso G, Giuffrida ML, Rizzarelli E
* Metallostasis And Amyloid Beta-Degrading Enzymes (1245 views)
Metallomics (ISSN: 1756-5901, 1756-591x, 1756-591xelectronic), 2012 Sep; 4(9): 937-949.
Impact Factor: 4.099
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Pappata S, Varrone A, Vicidomini C, Milan G, De Falco C, Sansone V, Iavarone A, Comerci M, Loré E, Panico M, Quarantelli M, Postiglione A, Salvatore M
* SPECT imaging of GABAA/benzodiazepine receptors and cerebral perfusion in mild cognitive impairment (588 views)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997), 2010 Jun; 37(6): 1156-1163.
Impact Factor: 5.036
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* Beta-Amyloid monomer and insulin/IGF-1 signaling in Alzheimer's disease (1943 views)
Mol Neurobiol (ISSN: 0893-7648), 2012 Dec; 46(3): 605-613.
Impact Factor: 5.471
View Export to BibTeX Export to EndNote
Grasso G, Giuffrida ML, Rizzarelli E
* Metallostasis And Amyloid Beta-Degrading Enzymes (1245 views)
Metallomics (ISSN: 1756-5901, 1756-591x, 1756-591xelectronic), 2012 Sep; 4(9): 937-949.
Impact Factor: 4.099
View Export to BibTeX Export to EndNote
Pappata S, Varrone A, Vicidomini C, Milan G, De Falco C, Sansone V, Iavarone A, Comerci M, Loré E, Panico M, Quarantelli M, Postiglione A, Salvatore M
* SPECT imaging of GABAA/benzodiazepine receptors and cerebral perfusion in mild cognitive impairment (588 views)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997), 2010 Jun; 37(6): 1156-1163.
Impact Factor: 5.036
View Export to BibTeX Export to EndNote
3 Records (3 excluding Abstracts).
Total impact factor: 14.606 (14.606 excluding Abstracts).
Total 5 year impact factor: 14.533 (14.533 excluding Abstracts).
Total impact factor: 14.606 (14.606 excluding Abstracts).
Total 5 year impact factor: 14.533 (14.533 excluding Abstracts).
525 views. Last view on Thursday 19 September 2024, 18:50:09
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