Browsing by Author "Quintanilla, RA"

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    Peroxisomal proliferation protects from β-amyloid neurodegeneration
    (2005) Santos, MJ; Quintanilla, RA; Toro, AS; Grandy, R; Dinamarca, MC; Godoy, JA; Inestrosa, NC
    Alzheimer disease is a neurodegenerative process that leads to severe cognitive impairment as a consequence of selective death of neuronal populations. The molecular pathogenesis of Alzheimer disease involves the participation of the beta-amyloid peptide (A beta) and oxidative stress. We report here that peroxisomal proliferation attenuated A beta-dependent toxicity in hippocampal neurons. Pretreatment with Wy-14.463 (Wy), a peroxisome proliferator, prevent the neuronal cell death and neuritic network loss induced by the A beta peptide. Moreover, the hippocampal neurons treated with this compound, showed an increase in the number of peroxisomes, with a concomitant increase in catalase activity. Additionally, we evaluate the Wy protective effect on beta-catenin levels, production of intracellular reactive oxygen species, cytoplasmic calcium uptake, and mitochondrial potential in hippocampal neurons exposed to H2O2 and A beta peptide. Results show that the peroxisomal proliferation prevents beta-catenin degradation, reactive oxygen species production, cytoplasmic calcium increase, and changes in mitochondrial viability. Our data suggest, for the first time, a direct link between peroxisomal proliferation and neuroprotection from A beta-induced degenerative changes.
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    Peroxisome proliferator-activated receptor gamma is expressed in hippocampal neurons and its activation prevents beta-amyloid neurodegeneration: role of Wnt signaling
    (ELSEVIER INC, 2005) Inestrosa, NC; Godoy, JA; Quintanilla, RA; Koenig, CS; Bronfman, M
    The molecular pathogenesis of Alzheimer's disease (AD) involves the participation of the amyloid-beta-peptide (Abeta), 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) PPARgamma is present in rat hippocampal neurons in culture. (2) Activation of PPAR-gamma by troglitazone and rosiglitazone protects rat hippocampal neurons against Abeta-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 Abeta-induced rise in bulk-free Ca2+. (4) PPARgamma activation results in the modulation of Wnt signaling components, including the inhibition of glycogen synthase kinase-3beta (GSK-3beta) and an increase of the cytoplasmic and nuclear beta-catenin levels. We conclude that the activation of PPARgamma prevents Abeta-induced neurodegeneration by a mechanism that may involve a cross talk between neuronal PPAR-y and the Writ signaling pathway. More important, the fact that the activation of PPAR-y attenuated Abeta-dependent neurodegeneration opens the possibility to fight AD from a new therapeutic perspective. (C) 2004 Published by Elsevier Inc.