Browsing by Author "Inestrosa, NC"

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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.
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    The N-terminal tandem repeat region of human prion protein reduces copper: Role of tryptophan residues
    (ACADEMIC PRESS INC, 2000) Ruiz, FH; Silva, E; Inestrosa, NC
    Prion protein (PrP) has attracted considerable attention, mainly due to its involvement in transmissible spongiform encephalopathies. Toward its N-terminal region, PrP bears an octapeptide repeat which has been shown to bind copper. We found that a human synthetic peptide (PrP59-91), corresponding to the four repeats of Pro-His-Gly-Gly-Gly-Trp-Gly-Gln has the ability to reduce copper, A mutant peptide lacking tryptophan displayed only 24% of the wild-type copper-reducing activity. Experiments performed in a N-2 environment confirmed that O-2 is not involved in the reaction. Our results indicated that cell surface PrP, besides its ability to bind copper, bears the capacity to reduce copper in vitro. The potential physiological role of copper reduction by PrP is discussed, (C) 2000 Academic Press.