Browsing by Author "Cerpa, W."

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    Hyperforin prevents β-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer's amyloid-β-deposits
    (2006) Dinamarca, M. C.; Cerpa, W.; Garrido, J.; Hancke, J. L.; Inestrosa, N. C.
    The major protein constituent of amyloid deposits in Alzheimer's disease (AD) is the amyloid beta-peptide (A beta). In the present work, we have determined the effect of hyperforin an acylphloroglucinol compound isolated from Hypericum perforatum (St John's Wort), on A beta-induced spatial memory impairments and on A beta neurotoxicity. We report here that hyperforin: ( 1) decreases amyloid deposit formation in rats injected with amyloid fibrils in the hippocampus; ( 2) decreases the neuropathological changes and behavioral impairments in a rat model of amyloidosis; ( 3) prevents A beta-induced neurotoxicity in hippocampal neurons both from amyloid fibrils and A beta oligomers, avoiding the increase in reactive oxidative species associated with amyloid toxicity. Both effects could be explained by the capacity of hyperforin to disaggregate amyloid deposits in a dose and time-dependent manner and to decrease A beta aggregation and amyloid formation. Altogether these evidences suggest that hyperforin may be useful to decrease amyloid burden and toxicity in AD patients, and may be a putative therapeutic agent to fight the disease.
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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.