We are interested in understanding the molecular pathogenesis of Alzheimer's disease (AD). In 1996, we proposed that the interactions of synaptic proteins with amyloid aggregates may be a key factor in the triggering of AD. In fact, we were able to establish that acetylcholinesterase and the amyloid-ß-peptide (Aß) form macromolecular complexes increasing neuronal toxicity. Later on, we found that amyloid neurotoxicity was partially mediated by H2O2 as well as by the loss of Wnt signaling. Attenuation of Wnt/ß-catenin signaling abrogates Aß neurotoxicity precisely in hippocampal neurons which are responsible for learning and memory. More recently we have been using APP transgenic mice in order to clarify the molecular mechanisms by which the Aß peptide interferes with the Wnt signaling pathway. More important, and because Alzheimer's entails a synaptic failure, we are strongly pursuing the study of the role of Wnt signaling in synaptic structure and function.
FONDAP-CRCP
Av. Bernardo O´Higgins 340 -
Santiago -
Región Metropolitana
Chile
Phone: 56-2-6862592 - Fax: 56-2-6862959
fondapni@bio.puc.cl
http://www.fondap-crcp.cl
Wnt signaling and Alzheimer disease. Cellular and molecular bases for Alzheimer disease