Acetylcholinesterase-amyloid-β-peptide interaction: Effect of Congo Red and the role of the Wnt pathway

Nibaldo C. Inestrosa, Alejandra Alvarez, Margarita C. Dinamarca, Tomás Pérez-Acle, Marcela Colombres

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

35 Citas (Scopus)


The cholinergic system impairment observed in Alzheimer's disease (AD) patients leads to the cognitive, global and behavioral dysfunction commonly associated with dementia. The only treatment for AD has been the use of inhibitors of acetylcholinesterase (AChE) (E.G., which is one of the several proteins associated with amyloid plaque deposits. Recently, novel dual inhibitors of AChE have been developed that target both the active site of the enzyme as well as the peripheral anionic site (PAS). Such inhibitors prevent the aggregation of amyloid-β-peptide (Aβ) into Alzheimer's fibrils. The incorporation of AChE, as a "chaperone" into amyloid aggregates results in the modification of the biochemical properties of the enzyme, including: sensitivity to low pH, inhibition at high substrate concentration, and increases of the Aβ neurotoxocity. Congo Red dye stabilizes the Aβ monomer, is able to inhibit oligomerization, and inhibits the binding of AChE to Aβ. However no effect of Congo Red on the binding of AChE to the Aβ preformed fibrils was observed. These studies suggest that different interactions between Aβ soluble-AChE and Aβ fibrils-AChE take place during the association between them. Docking studies were performed to evaluate the binding of Congo Red to Aβ in order to identify putative binding sites in the Aβ monomer that might interact with AChE. The binding site involves a region between residues 12 and 16. Finally, recent studies are consistent with the idea that a attenuating β-catenin loss of function of Wnt signaling components may play a role in the progression of neurodegenerative disease, such as AD, providing a connection between AChE-Aβ neurotoxicity and the Wnt signal transduction pathway.

Idioma originalInglés
Páginas (desde-hasta)301-306
Número de páginas6
PublicaciónCurrent Alzheimer Research
EstadoPublicada - jul 2005

Áreas temáticas de ASJC Scopus

  • Neurología clínica
  • Psiquiatría y salud mental
  • Psiquiatría biológica
  • Neurología


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