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Title: Peroxisome proliferator-activated receptor {gamma} is expressed in hippocampal neurons and its activation prevents {beta}-amyloid neurodegeneration: role of Wnt signaling

Abstract

The molecular pathogenesis of Alzheimer's disease (AD) involves the participation of the amyloid-{beta}-peptide (A{beta}), which plays a critical role in the neurodegeneration that triggers the disease. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, which are members of the nuclear receptor family. We report here that (1) PPAR{gamma} is present in rat hippocampal neurons in culture. (2) Activation of PPAR{gamma} by troglitazone and rosiglitazone protects rat hippocampal neurons against A{beta}-induced neurodegeneration, as shown by the 3-[4,5 -2yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay, immunofluorescence using an anti-heavy neurofilament antibody, and quantitative electron microscopy. (3) Hippocampal neurons treated with several PPAR{gamma} agonists, including troglitazone, rosiglitazone, and ciglitazone, prevent the excitotoxic A{beta}-induced rise in bulk-free Ca{sup 2+}. (4) PPAR{gamma} activation results in the modulation of Wnt signaling components, including the inhibition of glycogen synthase kinase-3{beta} (GSK-3{beta}) and an increase of the cytoplasmic and nuclear {beta}-catenin levels. We conclude that the activation of PPAR{gamma} prevents A{beta}-induced neurodegeneration by a mechanism that may involve a cross talk between neuronal PPAR{gamma} and the Wnt signaling pathway. More important, the fact that the activation of PPAR{gamma} attenuated A{beta}-dependent neurodegeneration opens the possibility to fight AD from a new therapeutic perspective.

Authors:
 [1];  [2];  [2];  [3];  [2]
  1. Centro FONDAP de Regulacion Celular y Patologia 'Joaquin V. Luco', Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile) and MIFAB, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile) and Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile)
  2. Centro FONDAP de Regulacion Celular y Patologia 'Joaquin V. Luco', Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile)
  3. Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile)
Publication Date:
OSTI Identifier:
20717550
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 304; Journal Issue: 1; Other Information: DOI: 10.1016/j.yexcr.2004.09.032; PII: S0014-4827(04)00573-7; Copyright (c) 2004 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BROMIDES; CALCIUM IONS; GLYCOGEN; NERVE CELLS; PEPTIDES; RATS; RECEPTORS; TRANSCRIPTION FACTORS

Citation Formats

Inestrosa, Nibaldo C, Godoy, Juan A, MIFAB, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Quintanilla, Rodrigo A, MIFAB, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Koenig, Cecilia S, Bronfman, Miguel, MIFAB, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, and Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago. Peroxisome proliferator-activated receptor {gamma} is expressed in hippocampal neurons and its activation prevents {beta}-amyloid neurodegeneration: role of Wnt signaling. United States: N. p., 2005. Web. doi:10.1016/j.yexcr.2004.09.032.
Inestrosa, Nibaldo C, Godoy, Juan A, MIFAB, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Quintanilla, Rodrigo A, MIFAB, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Koenig, Cecilia S, Bronfman, Miguel, MIFAB, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, & Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago. Peroxisome proliferator-activated receptor {gamma} is expressed in hippocampal neurons and its activation prevents {beta}-amyloid neurodegeneration: role of Wnt signaling. United States. https://doi.org/10.1016/j.yexcr.2004.09.032
Inestrosa, Nibaldo C, Godoy, Juan A, MIFAB, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Quintanilla, Rodrigo A, MIFAB, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Koenig, Cecilia S, Bronfman, Miguel, MIFAB, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, and Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago. 2005. "Peroxisome proliferator-activated receptor {gamma} is expressed in hippocampal neurons and its activation prevents {beta}-amyloid neurodegeneration: role of Wnt signaling". United States. https://doi.org/10.1016/j.yexcr.2004.09.032.
@article{osti_20717550,
title = {Peroxisome proliferator-activated receptor {gamma} is expressed in hippocampal neurons and its activation prevents {beta}-amyloid neurodegeneration: role of Wnt signaling},
author = {Inestrosa, Nibaldo C and Godoy, Juan A and MIFAB, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago and Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago and Quintanilla, Rodrigo A and MIFAB, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago and Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago and Koenig, Cecilia S and Bronfman, Miguel and MIFAB, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago and Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago},
abstractNote = {The molecular pathogenesis of Alzheimer's disease (AD) involves the participation of the amyloid-{beta}-peptide (A{beta}), which plays a critical role in the neurodegeneration that triggers the disease. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, which are members of the nuclear receptor family. We report here that (1) PPAR{gamma} is present in rat hippocampal neurons in culture. (2) Activation of PPAR{gamma} by troglitazone and rosiglitazone protects rat hippocampal neurons against A{beta}-induced neurodegeneration, as shown by the 3-[4,5 -2yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay, immunofluorescence using an anti-heavy neurofilament antibody, and quantitative electron microscopy. (3) Hippocampal neurons treated with several PPAR{gamma} agonists, including troglitazone, rosiglitazone, and ciglitazone, prevent the excitotoxic A{beta}-induced rise in bulk-free Ca{sup 2+}. (4) PPAR{gamma} activation results in the modulation of Wnt signaling components, including the inhibition of glycogen synthase kinase-3{beta} (GSK-3{beta}) and an increase of the cytoplasmic and nuclear {beta}-catenin levels. We conclude that the activation of PPAR{gamma} prevents A{beta}-induced neurodegeneration by a mechanism that may involve a cross talk between neuronal PPAR{gamma} and the Wnt signaling pathway. More important, the fact that the activation of PPAR{gamma} attenuated A{beta}-dependent neurodegeneration opens the possibility to fight AD from a new therapeutic perspective.},
doi = {10.1016/j.yexcr.2004.09.032},
url = {https://www.osti.gov/biblio/20717550}, journal = {Experimental Cell Research},
issn = {0014-4827},
number = 1,
volume = 304,
place = {United States},
year = {Thu Mar 10 00:00:00 EST 2005},
month = {Thu Mar 10 00:00:00 EST 2005}
}