Wnt-3a overcomes beta-amyloid toxicity in rat hippocampal neurons.
The aim of this study was to evaluate whether the direct activation of the Wnt signaling pathway by its endogenous Wnt-3a ligand prevents the toxic effects induced by amyloid-beta-peptide (Abeta) in rat hippocampal neurons. We report herein that the Wnt-3a ligand was indeed able to overcome toxic effects induced by Abeta in hippocampal neurons, including a neuronal impairment on cell survival, an increase in glycogen synthase kinase-3beta (GSK-3beta) and tau phosphorylation, a decrease in cytoplasmic beta-catenin and a decrease in the expression of the Wnt target gene engrailed-1. We further demonstrate that Wnt-3a protects hippocampal neurons from apoptosis induced by Abeta. Our results support the hypothesis that a loss of function of Wnt signaling may play a role in the progression of neurodegenerative diseases such as Alzheimer's disease.
Alvarez
Alejandra R
AR
Centro FONDAP de Regulación Celular y Patología "Joaquín V. Luco", MIFAB, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Godoy
Juan A
JA
Mullendorff
Karin
K
Olivares
Gonzalo H
GH
Bronfman
Miguel
M
Inestrosa
Nibaldo C
NC
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D018398:Homeodomain Proteins / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000819:agonists / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D051153:Wnt Proteins; D060508:Wnt3 Protein; D051176:beta Catenin; D016875:tau Proteins / Q000187:drug effects / Q000378:metabolism; D000099266:Engrailed 2 Protein
D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D018398:Homeodomain Proteins; D008024:Ligands; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011506:Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D060508:Wnt3 Protein; D051176:beta Catenin; D016875:tau Proteins; D000099266:Engrailed 2 Protein; C495268:Ctnnb1 protein, rat; C000605508:Gsk3b protein, rat