Acetylcholinesterase-amyloid-?-peptide interaction and Wnt signaling involvement in A? neurotoxicity

Inestrosa, N. C.; Alvarez A.; Godoy, J; Reyes A.; De Ferrari G.V.

Keywords: model, proteins, rat, simulation, amyloid, animals, rats, protein, cell, disease, histopathology, beta, neurotoxicity, metabolism, surgery, experiment, transduction, male, genetics, lithium, fetus, immunofluorescence, interaction, pathophysiology, image, acetylcholinesterase, tissue, hippocampus, zebrafish, signal, beta-protein, computer, pathology, article, precursor, wnt, alzheimer, oncoprotein, analysis, plaque, controlled, animal, plaques, study, nonhuman, Rats,, Sprague-Dawley, Sprague, Dawley, Proto-Oncogene, stereotaxic, Neurofilament, thioflavine, senile, Neurofibrils


Previous studies have indicated that acetylcholinesterase (AChE) promotes amyloid-?-peptide (A?) fibril formation and AChE-A? complexes increase A?-dependent neurotoxicity. Here we present evidence for the: i) identification of the AChE motif that promotes amyloid formation, ii) in vivo effect of AChE on brain plaque formation, and iii) connection between AChE-A? neurotoxicity and the Wnt signal transduction pathway. Computer modeling, stereotaxic infusions and cell biological techniques were used to study the above problems. Results indicated that a 3.4 kDa AChE peptide promotes A? fibril formation. AChE infusion into rat hippocampus determines the appearance of anti-A? and thioflavine-S positive plaques, and AChE-A? toxicity on hippocampal cultures was blocked by lithium, an activator of the Wnt cascade. We suggest that AChE-A?/A? dependent neurotoxicity may result in loss of function of Wnt signaling components, and open the possibility that lithium may be considered as a candidate for therapeutic intervention in Alzheimer's disease pathology.

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Título según SCOPUS: Acetylcholinesterase-amyloid-?-peptide interaction and Wnt signaling involvement in A? neurotoxicity
Título de la Revista: Acta Neurologica Scandinavica, Supplement
Volumen: 102
Número: 176
Editorial: Wiley-Blackwell
Fecha de publicación: 2000
Página de inicio: 53
Página final: 59
Idioma: English