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Title

The Vitamin A Derivative All-Trans Retinoic Acid Repairs Amyloid-β-Induced Double-Strand Breaks in Neural Cells and in the Murine Neocortex

Authors
Allioux, Clélia
Leuba, Geneviève
Published in Neural Plasticity. 2016, vol. 2016
Abstract The amyloid-𝛽 peptide or A𝛽 is the key player in the amyloid-cascade hypothesis of Alzheimer’s disease. A𝛽 appears to trigger cell death but also production of double-strand breaks (DSBs) in aging and Alzheimer’s disease. All-trans retinoic acid (RA), a derivative of vitamin A, was already known for its neuroprotective effects against the amyloid cascade. It diminishes, for instance, the production of A𝛽 peptides and their oligomerisation. In the present work we investigated the possible implication of RA receptor (RAR) in repair of A𝛽-induced DSBs. We demonstrated that RA, as well as RAR agonist Am80, but not AGN 193109 antagonist, repair A𝛽-induced DSBs in SH-SY5Y cells and an astrocytic cell line as well as in the murine cortical tissue of young and aged mice. The nonhomologous end joining pathway and the Ataxia Telangiectasia Mutated kinase were shown to be involved in RA- mediated DSBs repair in the SH-SY5Y cells. Our data suggest that RA, besides increasing cell viability in the cortex of young and even of aged mice, might also result in targeted DNA repair of genes important for cell or synaptic maintenance. This phenomenon would remain functional up to a point when A𝛽 increase and RA decrease probably lead to a pathological state.
Keywords All-trans retinoic acidAmyloid-𝛽 peptideAstrocytesC57BL/6J miceCell viabilityDNA repairDouble-strand breaksNeocortexRetinoic acid-mediated double-strand breaks repairSH-SY5Y cellsVitamin A
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Research group HUG Unité de Biomarqueurs de vulnérabilité
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GRUZ-GIBELLI DA MOUTA, Emmanuelle et al. The Vitamin A Derivative All-Trans Retinoic Acid Repairs Amyloid-β-Induced Double-Strand Breaks in Neural Cells and in the Murine Neocortex. In: Neural Plasticity, 2016, vol. 2016. https://archive-ouverte.unige.ch/unige:80007

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Deposited on : 2016-01-25

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