Browsing by Author "Varela-Nallar, L."

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    Induction of Cellular Prion Protein Gene Expression by Copper in Neurons
    (2006) Varela-Nallar, L.; Larrondo Castro, Luis Fernando; Inestrosa Cantín, Nibaldo
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    Role of Copper in Prion Diseases: Deleterious or Beneficial?
    (2006) Varela-Nallar, L.; González de la Rosa, Alfonso; Inestrosa Cantín, Nibaldo
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    Tetrahydrohyperforin prevents cognitive deficit, Aβ deposition, tau phosphorylation and synaptotoxicity in the APPswe/PSEN1ΔE9 model of Alzheimer's disease: a possible effect on APP processing
    (2011) Inestrosa, N. C.; Tapia-Rojas, C.; Griffith, T. N.; Carvajal, F. J.; Benito, M. J.; Rivera-Dictter, A.; Alvarez, A. R.; Serrano, F. G.; Hancke, J. L.; Burgos, P. V.; Parodi, J.; Varela-Nallar, L.
    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, amyloid-beta peptide (A beta) accumulation and synaptic alterations. Previous studies indicated that hyperforin, a component of the St John's Wort, prevents A beta neurotoxicity and some behavioral impairments in a rat model of AD. In this study we examined the ability of tetrahydrohyperforin (IDN5607), a stable hyperforin derivative, to prevent the cognitive deficit and synaptic impairment in an in vivo model of AD. In double transgenic APPswe/PSEN1DE9 mice, IDN5706 improves memory and prevents the impairment of synaptic plasticity in a dose-dependent manner, inducing a recovery of long-term potentiation. In agreement with these findings, IDN5706 prevented the decrease in synaptic proteins in hippocampus and cortex. In addition, decreased levels of tau hyperphosphorylation, astrogliosis, and total fibrillar and oligomeric forms of A beta were determined in double transgenic mice treated with IDN5706. In cultured cells, IDN5706 decreased the proteolytic processing of the amyloid precursor protein that leads to A beta peptide generation. These findings indicate that IDN5706 ameliorates AD neuropathology and could be considered of therapeutic relevance in AD treatment.
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    Wnt signaling in the regulation of adult hippocampal neurogenesis
    (2013) Varela-Nallar, L.; Inestrosa Cantín, Nibaldo
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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.