Abstract
Deterioration of the cortical cholinergic system is a leading neurochemical feature of Alzheimer’s Disease (AD). This review summarizes evidence that the homomeric α7- nicotinic acetylcholine receptor (nAChR) plays a crucial role in the pathogenesis of this disease, which is characterized by amyloid-β (Aβ) accumulations and neurofibrillary tangles originating from of hyperphosphorylated tau protein. Aβ binds to α7-nAChRs with a high affinity, either activating or inhibiting this receptor in a concentration-dependent manner. There is strong evidence that α7-nAChRs are neuroprotective, reducing Aβ-induced toxicity; but co-localization of α7- nAChRs, Aβ and amyloid plaques also points to neurodegenerative actions. Aβ induces tau phosphorylation via α7-nAChR activation. Aβ influences hippocampus-dependent memory and long-term potentiation in a dose-dependent way: there is evidence that enhancement by picomolar Aβ concentrations is mediated by α7-nAChRs, whereas inhibition by nanomolar concentrations is independent of nAChRs and probably mediated by small Aβ42 oligomers. α7-nAChRs located on vascular smooth muscle cells and astrocytes are also involved in the pathogenesis of AD. Although these data strongly point to an important role of α7-nAChRs in the development of AD, dose-dependence of the effects, rapid desensitization of the receptor and dependence of the effects on Aβ aggregation (monomers, oligomers, fibrils) make it difficult to develop simple therapeutic strategies acting upon this receptor.
Keywords: Acetylcholinesterase, amyloid, Alzheimer’s Disease, cholinergic, hippocampus, neuroprotection, nicotinic acetylcholine receptor, review, tau phosphorylation.
Current Alzheimer Research
Title:On the Interaction of β-Amyloid Peptides and α7-Nicotinic Acetylcholine Receptors in Alzheimer’s Disease
Volume: 10 Issue: 6
Author(s): Murat Oz, Dietrich E. Lorke, Keun-Hang S. Yang and Georg Petroianu
Affiliation:
Keywords: Acetylcholinesterase, amyloid, Alzheimer’s Disease, cholinergic, hippocampus, neuroprotection, nicotinic acetylcholine receptor, review, tau phosphorylation.
Abstract: Deterioration of the cortical cholinergic system is a leading neurochemical feature of Alzheimer’s Disease (AD). This review summarizes evidence that the homomeric α7- nicotinic acetylcholine receptor (nAChR) plays a crucial role in the pathogenesis of this disease, which is characterized by amyloid-β (Aβ) accumulations and neurofibrillary tangles originating from of hyperphosphorylated tau protein. Aβ binds to α7-nAChRs with a high affinity, either activating or inhibiting this receptor in a concentration-dependent manner. There is strong evidence that α7-nAChRs are neuroprotective, reducing Aβ-induced toxicity; but co-localization of α7- nAChRs, Aβ and amyloid plaques also points to neurodegenerative actions. Aβ induces tau phosphorylation via α7-nAChR activation. Aβ influences hippocampus-dependent memory and long-term potentiation in a dose-dependent way: there is evidence that enhancement by picomolar Aβ concentrations is mediated by α7-nAChRs, whereas inhibition by nanomolar concentrations is independent of nAChRs and probably mediated by small Aβ42 oligomers. α7-nAChRs located on vascular smooth muscle cells and astrocytes are also involved in the pathogenesis of AD. Although these data strongly point to an important role of α7-nAChRs in the development of AD, dose-dependence of the effects, rapid desensitization of the receptor and dependence of the effects on Aβ aggregation (monomers, oligomers, fibrils) make it difficult to develop simple therapeutic strategies acting upon this receptor.
Export Options
About this article
Cite this article as:
Oz Murat, Lorke E. Dietrich, Yang S. Keun-Hang and Petroianu Georg, On the Interaction of β-Amyloid Peptides and α7-Nicotinic Acetylcholine Receptors in Alzheimer’s Disease, Current Alzheimer Research 2013; 10 (6) . https://dx.doi.org/10.2174/15672050113109990132
DOI https://dx.doi.org/10.2174/15672050113109990132 |
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
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
Diagnostic and therapeutic biomarkers of dementia
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
- 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
-
Managing Expectations in the Transition to Proof of Concept Studies
Reviews on Recent Clinical Trials Targeting Aurora Kinases in Cancer Treatment
Current Drug Targets Eremurus spectabilis, Rich Source of Isoorientin: Isolation, Quantification and Anti-Cancer Activity on SH-SY5Y Neuroblastoma Cells
Current Pharmaceutical Analysis Crocetin: an Agent Derived from Saffron for Prevention and Therapy for Cancer
Current Pharmaceutical Biotechnology Inhibitors of the Ubiquitin-Proteasome System and the Cell Death Machinery: How Many Pathways are Activated?
Current Molecular Pharmacology Isolation, Purification, Characterisation and Application of L-ASNase: A Review
Recent Patents on Biotechnology AChE Inhibition-based Multi-target-directed Ligands, a Novel Pharmacological Approach for the Symptomatic and Disease-modifying Therapy of Alzheimer’s Disease
Current Neuropharmacology NPY and NPY Receptors in Vascular Remodeling
Current Topics in Medicinal Chemistry Lipoxygenase (LOX) Pathway: A Promising Target to Combat Cancer
Current Pharmaceutical Design Recent Patents in Circulating Cell-Free Tumor DNA as Biomarker in Cancer
Recent Patents on Biomarkers Modulation of the Cannabinoid System: A New Perspective for the Treatment of the Alzheimer’s Disease
Current Neuropharmacology Conformational Changes of Prion Protein and Nucleic Acid Arising from their Interaction and Relation of the Altered Structures in Causing Prion Disease
Mini-Reviews in Medicinal Chemistry Raman Spectroscopy and Imaging: Promising Optical Diagnostic Tools in Pediatrics
Current Medicinal Chemistry Recent Advances in Phenanthroindolizidine and Phenanthroquinolizidine Derivatives with Anticancer Activities
Anti-Cancer Agents in Medicinal Chemistry Therapy in Prion Diseases
Current Topics in Medicinal Chemistry The Dual Role of Nitric Oxide in Glioma
Current Pharmaceutical Design Electrochemical DNA Biosensors in Drug Analysis
Current Pharmaceutical Analysis Derivatives of Procaspase-Activating Compound 1 (PAC-1) and their Anticancer Activities
Current Medicinal Chemistry Pharmacogenomics of Breast Cancer Targeted Therapy: Focus on Recent Patents
Recent Patents on DNA & Gene Sequences Melatonin as Antioxidant Under Pathological Processes
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery