Abstract
The review examines the multifaceted interactions between cholinergic transmission and beta-amyloid suggesting a continuum in the action of the peptide that at low concentrations (picomolar-low nanomolar) may directly stimulate nicotinic cholinergic receptor while desensitizing them at increasing concentrations (high nanomolar-low micromolar). In addition high beta-amyloid concentrations may reduce the synaptic release of several neurotransmitters, including glutamate, aspartate, GABA, glycine and dopamine, when the release is elicited through cholinergic stimulation but not following depolarization. The effect of beta-amyloid has been observed both in vitro and in vivo in at least three different brain areas (nucleus accumbens, striatum, hippocampus) suggesting that the peptide may exert some general effects even if not all the brain areas have been evaluated. In turn the activation of cholinergic receptors may affect the amyloid precursor protein processing diverting the metabolism toward non-amyloidogenic products. These actions, dissociated from those described in the case of high beta-amyloid concentrations leading to neurotoxic oligomers, may participate to cause dysfunctions in the neurotransmitter activity, in turn leading, at least from a theoretical point of view, to early neuropsychiatric disturbances in the disease. Complexively these observations underscore novel relationships between two main players in Alzheimer's disease pathogenesis that are beta-amyloid and cholinergic transmission. Also emerges the inherent difficulty of targeting beta-amyloid in a context in which the peptide exerts several actions beyond neurotoxicity.
Keywords: Alzheimer's disease, beta-amyloid, cholinergic neurotransmission, nicotinic receptors, neurotransmitters.
Current Pharmaceutical Design
Title:Dangerous Liaisons between Beta-Amyloid and Cholinergic Neurotransmission
Volume: 20 Issue: 15
Author(s): Stefano Govoni, Elisa Mura, Stefania Preda, Marco Racchi, Cristina Lanni, Massimo Grilli, Stefania Zappettini, Alessia Salamone, Guendalina Olivero, Anna Pittaluga and Mario Marchi
Affiliation:
Keywords: Alzheimer's disease, beta-amyloid, cholinergic neurotransmission, nicotinic receptors, neurotransmitters.
Abstract: The review examines the multifaceted interactions between cholinergic transmission and beta-amyloid suggesting a continuum in the action of the peptide that at low concentrations (picomolar-low nanomolar) may directly stimulate nicotinic cholinergic receptor while desensitizing them at increasing concentrations (high nanomolar-low micromolar). In addition high beta-amyloid concentrations may reduce the synaptic release of several neurotransmitters, including glutamate, aspartate, GABA, glycine and dopamine, when the release is elicited through cholinergic stimulation but not following depolarization. The effect of beta-amyloid has been observed both in vitro and in vivo in at least three different brain areas (nucleus accumbens, striatum, hippocampus) suggesting that the peptide may exert some general effects even if not all the brain areas have been evaluated. In turn the activation of cholinergic receptors may affect the amyloid precursor protein processing diverting the metabolism toward non-amyloidogenic products. These actions, dissociated from those described in the case of high beta-amyloid concentrations leading to neurotoxic oligomers, may participate to cause dysfunctions in the neurotransmitter activity, in turn leading, at least from a theoretical point of view, to early neuropsychiatric disturbances in the disease. Complexively these observations underscore novel relationships between two main players in Alzheimer's disease pathogenesis that are beta-amyloid and cholinergic transmission. Also emerges the inherent difficulty of targeting beta-amyloid in a context in which the peptide exerts several actions beyond neurotoxicity.
Export Options
About this article
Cite this article as:
Govoni Stefano, Mura Elisa, Preda Stefania, Racchi Marco, Lanni Cristina, Grilli Massimo, Zappettini Stefania, Salamone Alessia, Olivero Guendalina, Pittaluga Anna and Marchi Mario, Dangerous Liaisons between Beta-Amyloid and Cholinergic Neurotransmission, Current Pharmaceutical Design 2014; 20 (15) . https://dx.doi.org/10.2174/13816128113199990503
DOI https://dx.doi.org/10.2174/13816128113199990503 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Iron Chelating Strategies in Systemic Metal Overload, Neurodegeneration and Cancer
Current Medicinal Chemistry Targeting the Renin-angiotensin System: Whats New?
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Pathogenesis of Diabetic Retinopathy and Diabetic Macular Edema and Enzyme Inhibition
Current Enzyme Inhibition The Application of Angiotensin Converting Enzyme Inhibitors in Heart Surgery
Letters in Drug Design & Discovery Treatment of Inflammatory and Paraproteinemic Neuropathies
Current Drug Targets - Immune, Endocrine & Metabolic Disorders NO News is not Necessarily Good News in Cancer
Current Cancer Drug Targets Different Generations of Type-B Monoamine Oxidase Inhibitors in Parkinson’s Disease: From Bench to Bedside
Current Neuropharmacology The Impact of Combination Therapy with a-Blockers and 5ARIs on the Progression of BPH
Current Drug Targets Effect of Nitric Oxide Synthase Inhibition on Body Temperature Control During Endotoxemic Shock
Current Enzyme Inhibition Hydrolyzates of Silkworm Pupae (Bombyx Mori) Protein is a New Source of Angiotensin I-Converting Enzyme Inhibitory Peptides(ACEIP)
Current Pharmaceutical Biotechnology L-Arginine Transport and Nitric Oxide Production in Kinin Receptor B1-/- Endothelial Cells.
Protein & Peptide Letters Phytochemical Therapies in Vascular Functioning: A Molecular Approach
Current Vascular Pharmacology Pulmonary Embolism Response Team (PERT) - A New Paradigm for the Treatment of Pulmonary Embolism
Current Pharmaceutical Design Skeletal Effects of Central Nervous System Active Drugs: Anxiolytics, Sedatives, Antidepressants, Lithium and Neuroleptics
Current Drug Safety Phosphodiesterase 5 Inhibitors in the Treatment of Erectile Dysfunction
Current Pharmaceutical Design Altered CYP Expression and Function in Response to Dietary Factors: Potential Roles in Disease Pathogenesis
Current Drug Metabolism Molecular Basis of Mineralocorticoid Receptor Action in the Nervous System
CNS & Neurological Disorders - Drug Targets C5a, a Therapeutic Target in Sepsis
Recent Patents on Anti-Infective Drug Discovery Synthesis of Some New Chromeno[2,3-b]pyridine and [1,2,4]Triazolo[1,5- a]quinoline Nucleoside Analogues with Expected Biological Activity
Letters in Organic Chemistry Relaxin as a Cardiovascular Hormone: Physiology, Pathophysiology and Therapeutic Promises
Cardiovascular & Hematological Agents in Medicinal Chemistry