Abstract
The cholinergic system impairment observed in Alzheimers 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.C. 3.1.1.7), 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 Alzheimers 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 Ab 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 Ab 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.
Keywords: acetylcholinesterase, alzheimers disease, amyloid peptide, congo red, peripheral anionic site
Current Alzheimer Research
Title: Acetylcholinesterase-Amyloid-β-peptide Interaction: Effect of Congo Red and the Role of the Wnt Pathway
Volume: 2 Issue: 3
Author(s): Nibaldo C. Inestrosa, Alejandra Alvarez, Margarita C. Dinamarca, Tomas Perez-Acle and Marcela Colombres
Affiliation:
Keywords: acetylcholinesterase, alzheimers disease, amyloid peptide, congo red, peripheral anionic site
Abstract: The cholinergic system impairment observed in Alzheimers 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.C. 3.1.1.7), 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 Alzheimers 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 Ab 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 Ab 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.
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Inestrosa C. Nibaldo, Alvarez Alejandra, Dinamarca C. Margarita, Perez-Acle Tomas and Colombres Marcela, Acetylcholinesterase-Amyloid-β-peptide Interaction: Effect of Congo Red and the Role of the Wnt Pathway, Current Alzheimer Research 2005; 2 (3) . https://dx.doi.org/10.2174/1567205054367928
DOI https://dx.doi.org/10.2174/1567205054367928 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
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Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
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