Alzheimer's disease-associated neurotoxic peptide amyloid-ß impairs base excision repair in human neuroblastoma cells.
Int J Mol Sci
; 13(11): 14766-87, 2012 Nov 13.
Article
em En
| MEDLINE
| ID: mdl-23203093
ABSTRACT
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-ß (Aß), which is known to generate oxidative stress. In this study, we showed that the presence of Aß 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 Aß-mediated perturbation of DNA damage/repair systems in the "Aß cell line". Taken together, these findings indicate that Aß 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
/
Reparo do DNA
/
Neuroblastoma
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
França