title: The Vitamin A Derivative All-Trans Retinoic Acid Repairs Amyloid-β-Induced Double-Strand Breaks in Neural Cells and in the Murine Neocortex.
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.
authors.affiliation: Department of Psychiatry, University Hospital Geneva, Chêne-Bourg, 1225 Geneva, Switzerland.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Gruz-Gibelli
authors.affiliation: Department of Psychiatry, University Hospital Geneva, Chêne-Bourg, 1225 Geneva, Switzerland.
authors.forename: Natacha
authors.initials: N
authors.lastname: Chessel
authors.affiliation: Department of Psychiatry, University Hospital Geneva, Chêne-Bourg, 1225 Geneva, Switzerland.
authors.forename: Clélia
authors.initials: C
authors.lastname: Allioux
authors.affiliation: Department of Psychiatry, University Hospital Geneva, Chêne-Bourg, 1225 Geneva, Switzerland.
authors.forename: Pascale
authors.initials: P
authors.lastname: Marin
authors.affiliation: Department of Psychiatry, University Hospital Geneva, Chêne-Bourg, 1225 Geneva, Switzerland.
authors.forename: Françoise
authors.initials: F
authors.lastname: Piotton
authors.affiliation: Center for Psychiatric Neuroscience, Department of Psychiatry, CHUV, 1008 Lausanne-Prilly, Switzerland.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Leuba
authors.affiliation: Department of Internal Medicine, Rehabilitation and Geriatrics, University Hospital of Geneva and University of Geneva, Thônex, 1226 Geneva, Switzerland.
authors.forename: François R
authors.initials: FR
authors.lastname: Herrmann
authors.affiliation: Department of Psychiatry, University Hospital Geneva, Chêne-Bourg, 1225 Geneva, Switzerland; Geneva Neuroscience Center, Geneva University, 1211 Geneva, Switzerland.
authors.forename: Armand
authors.initials: A
authors.lastname: Savioz
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000633:toxicity*; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D014801:Vitamin A; D014212:Tretinoin