Abstract
Alzheimers disease (AD) is characterized by selective neuronal cell death, which is probably caused by amyloid b-peptide (Aβ) oligomers and fibrils. We have found that acetylcholinesterase (AChE), a senile plaque component, increases amyloid fibril assembly with the formation of highly toxic complexes (Aβ-AChE). The neurotoxic effect induced by Aβ-AChE complexes was higher than that induced by the Aβ peptide alone as shown both in vitro (hippocampal neurons) and in vivo (rats injected with Ab peptide in the dorsal hippocampus). Interestingly, treatment with Aβ-AChE complexes decreases the cytoplasmic β-catenin level, a key component of Wnt signaling. Conversely, the activation of this signaling pathway by Wnt-3a promotes neuronal survival and rescues changes in Wnt components (activation or subcellular localization). Moreover Frzb-1, a Wnt antagonist reverses the Wnt-3a neuroprotection effect against Aβ neurotoxicity. Compounds that mimic the Wnt signaling or modulate the cross-talking with this pathway could be used as neuroprotective agents for therapeutic strategies in AD patients.
Keywords: ache activity, neurodegenerative processes, brain, amyloid fibrils, hippocampal neurons, signaling pathway, g-catenin, gsk
Current Alzheimer Research
Title: Acetylcholinesterase (AChE) - Amyloid-β-Peptide Complexes in Alzheimers Disease. The Wnt Signaling Pathway
Volume: 1 Issue: 4
Author(s): Nibaldo C. Inestrosa, Soledad Urra and Marcela Colombres
Affiliation:
Keywords: ache activity, neurodegenerative processes, brain, amyloid fibrils, hippocampal neurons, signaling pathway, g-catenin, gsk
Abstract: Alzheimers disease (AD) is characterized by selective neuronal cell death, which is probably caused by amyloid b-peptide (Aβ) oligomers and fibrils. We have found that acetylcholinesterase (AChE), a senile plaque component, increases amyloid fibril assembly with the formation of highly toxic complexes (Aβ-AChE). The neurotoxic effect induced by Aβ-AChE complexes was higher than that induced by the Aβ peptide alone as shown both in vitro (hippocampal neurons) and in vivo (rats injected with Ab peptide in the dorsal hippocampus). Interestingly, treatment with Aβ-AChE complexes decreases the cytoplasmic β-catenin level, a key component of Wnt signaling. Conversely, the activation of this signaling pathway by Wnt-3a promotes neuronal survival and rescues changes in Wnt components (activation or subcellular localization). Moreover Frzb-1, a Wnt antagonist reverses the Wnt-3a neuroprotection effect against Aβ neurotoxicity. Compounds that mimic the Wnt signaling or modulate the cross-talking with this pathway could be used as neuroprotective agents for therapeutic strategies in AD patients.
Export Options
About this article
Cite this article as:
Inestrosa C. Nibaldo, Urra Soledad and Colombres Marcela, Acetylcholinesterase (AChE) - Amyloid-β-Peptide Complexes in Alzheimers Disease. The Wnt Signaling Pathway, Current Alzheimer Research 2004; 1 (4) . https://dx.doi.org/10.2174/1567205043332063
DOI https://dx.doi.org/10.2174/1567205043332063 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
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
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...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
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Pathogenesis of Abeta Oligomers in Synaptic Failure
Current Alzheimer Research Neuroprotective Role of Natural Polyphenols
Current Topics in Medicinal Chemistry Serum Starvation Induces BACE1 Processing and Secretion
Current Alzheimer Research Infrared-Spectroscopy: A Non-Invasive Tool for Medical Diagnostics and Drug Analysis
Current Medicinal Chemistry Impact and Therapeutic Potential of PPARs in Alzheimers Disease
Current Neuropharmacology Advances in Structural Modifications and Biological Activities of Berberine: An Active Compound in Traditional Chinese Medicine
Mini-Reviews in Medicinal Chemistry Patent Annotations
Recent Patents on Anti-Cancer Drug Discovery Improved Brain Expression of Anti-Amyloid β scFv by Complexation of mRNA Including a Secretion Sequence with PEG-based Block Catiomer
Current Alzheimer Research Resveratrol and Analogues: A Review of Antioxidant Activity and Applications to Human Health
Recent Patents on Food, Nutrition & Agriculture Editorial [Hot Topic: Drug Targets in Alzheimers Disease (Executive Editors: G. Munch and G. Stuchbury)]
Current Pharmaceutical Design MTDL Design Strategy in the Context of Alzheimers Disease: From Lipocrine to Memoquin and Beyond
Current Pharmaceutical Design Serotonin Reuptake Inhibitors and Cardiovascular Disease
Vascular Disease Prevention (Discontinued) Quantitative Machine Learning Analysis of Brain MRI Morphology throughout Aging
Current Aging Science Obstructive Sleep Apnoea Syndrome and Diabetes. Fortuitous Association or Interaction?
Current Diabetes Reviews Preventive and Protective Roles of Dietary Nrf2 Activators Against Central Nervous System Diseases
CNS & Neurological Disorders - Drug Targets Locus (Coeruleus) Minoris Resistentiae in Pathogenesis of Alzheimer’s Disease
Current Alzheimer Research Clearance of Amyloid-β Peptide by Neuronal and Non-Neuronal Cells: Proteolytic Degradation by Secreted and Membrane associated Proteases
Current Neurovascular Research Bipolar Affective Disorder, Epilepsy and Migraine – Does Possible Shared Pathogenesis Explain their Association?
Current Psychopharmacology Current Therapeutic Molecules and Targets in Neurodegenerative Diseases Based on in silico Drug Design
Current Neuropharmacology The Ability of Tolfenamic Acid to Penetrate the Brain: A Model for Testing the Brain Disposition of Candidate Alzheimers Drugs Using Multiple Platforms
Current Alzheimer Research