Browsing by Author "Godoy, J.A."

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    Peroxisomal proliferation protects from β-amyloid neurodegeneration
    (2005) Santos, M.J.; Quintanilla, R.A.; Toro, A.S.; Grandy, R.; Dinamarca, M.C.; Godoy, J.A.; Inestrosa, N.C.
    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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    Wnt signaling modulates pre- and postsynaptic maturation: therapeutic considerations
    (2010) Farías, G.G.; Godoy, J.A.; Cerpa, W.; Varela-Nallar, L.; Inestrosa, N.C.
    Wnt signaling regulates a wealth of aspects of nervous system development and function in embryonic stages and in adulthood. The expression of Wnt ligands and components of the Wnt signaling machinery in early stages of neural development has been related to its role in neurite patterning and in synaptogenesis. Moreover, its expression in the mature nervous system suggests a role for this pathway in synaptic maintenance and function. Therefore, it is of crucial relevance the understanding of the mechanisms by which Wnt signaling regulates these processes. Herein, we discuss how different Wnt ligands, acting through different Wnt signaling pathways, operate in pre- and postsynaptic regions to modulate synapse structure and function. We also elaborate on the idea that Wnt signaling pathways are a target for the treatment of neurodegenerative diseases that affect synaptic integrity, such as Alzheimer's disease. Developmental Dynamics 239:94–101, 2010. © 2009 Wiley-Liss, Inc.