Effects of the Alzheimer's disease-associated Amyloid-β peptide on the DNA repair systems
type: Dataset
description: Alzheimer's disease (AD) is an age-related neurodegenerative disorder which leads to a progressive and irreversible loss of cognitive and behavioral functions. Two major pathological hallmarks are affecting patients with AD: intracellular neurofibrillary tangles (mostly constituted of the hyperphosphorylated Tau protein) and extracellular senile plaques deposits (mostly constituted of the amyloid- β peptide (Aβ)). If the complex etiology of AD remains to be defined, the role played by oxidative stress (partly generated by Aβ) is widely accepted. Thus, it has been proposed that the neuronal death in AD could be due to the accumulation of oxidative DNA damage over life that could be moreover associated to a deficient DNA repair capacity. In this study we focused on the Aβ peptide specific effects on DNA repair systems. We worked on a human neuroblastoma cell line which possesses the ability to secrete the Aβ to a very physiological level. In this model, we observed an increase in oxidative DNA damage, under basal conditions and even more following exposure to a metallic or oxidative stress. Surprinsingly, the oxidative lesions-associated BER system, appeared to be downregulated in the presence of Aβ, and to a greater extent diminished after stress. These observations suggest that the Aβ-secreting cell line is not able to respond to a harmful environment, which is likely to trigger the accumulation of oxidative DNA damage. The other highlight of this work is the over-expression of generally NER-associated proteins, in the presence of Aβ coupled to an oxidative stress. These proteins exhibit a multifunctionnality within cells and their stimulation could reveal the set up of an apoptotic pathway rather than the induction of a DNA repair process. Taken together, these results lead us to establish for the first time a strong link between Aβ secretion and the impairment of DNA repair capacities, which are inclined to cause the neuronal death that is observed in excess in AD…
landing page: https://theses.hal.science/tel-00680083
identifier: NNT: 2011GRENV067
keyword: 8oxog
keyword: abeta-peptide
keyword: alzheimer
keyword: dna-damages
keyword: infoeu-reposemanticsdoctoralthesis
keyword: lesions-de-ladn
keyword: ogg1
keyword: oxidative-stress
keyword: peptide-a
keyword: sdvotlife-sciences-q-bioother-q-bioot
keyword: stress-oxydant
keyword: theses
issued: 2026-05-24T08:35:44.984399
modified: 2026-05-24T08:35:44.984408
language: fr
contact point: Organization
  fn: CCSD

test_moissonnage_selune
type: Agent

Effects of the Alzheimer's disease-associated Amyloid-β peptide on the DNA repair systems
type: Distribution
format: HTML
access URL: https://theses.hal.science/tel-00680083
issued: 2026-05-24T08:35:44.989559
modified: 2026-05-24T08:35:44.939251