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Acetylcholinesterase–amyloid‐β‐peptide interaction and Wnt signaling involvement in Aβ neurotoxicity
Author(s) -
Inestrosa N. C.,
Alvarez A.,
Godoy J.,
Reyes A.,
De Ferrari G. V.
Publication year - 2000
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1034/j.1600-0404.2000.00308.x
Subject(s) - acetylcholinesterase , neurotoxicity , wnt signaling pathway , aché , chemistry , microbiology and biotechnology , signal transduction , biochemistry , toxicity , biology , enzyme , organic chemistry
Previous studies have indicated that acetylcholinesterase (AChE) promotes amyloid‐β‐peptide (Aβ) fibril formation and AChE‐Aβ complexes increase Aβ‐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‐Aβ 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 Aβ fibril formation. AChE infusion into rat hippocampus determines the appearance of anti‐Aβ and thioflavine‐S positive plaques, and AChE‐Aβ toxicity on hippocampal cultures was blocked by lithium, an activator of the Wnt cascade. We suggest that AChE‐Aβ/Aβ 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.