Abstract
The cholinergic hypothesis of decline in dementia, whereby deficits in learning, memory and behavior are caused, at least in part, by decreased levels of acetylcholine (ACh) in the brain, first emerged more than 20 years ago. The role for acetylcholinesterase (AChE) and its inhibition in this scheme has long been accepted, but findings from preclinical experiments and clinical trials have placed butyrylcholinesterase (BuChE) alongside AChE as an important contributor to the occurrence, symptoms, progression and responses to treatment in dementia. A number of new lines of evidence suggest that both cholinesterase inhibitors (ChEs) may have broader functions in the CNS than previously thought, which relate to both classical esterase activities of the enzymes as well as non-classical actions unrelated to their enzymatic function. Data suggest involvement of the ChEs in modulating glial activation, cerebral blood flow, the amyloid cascade, and tau phosphorylation. It has therefore been speculated that some actions of the ChEs could affect the underlying disease processes in Alzheimers disease (AD), and that pharmacological manipulation with ChE inhibitors may affect longterm disease progression. Focusing on new findings relating to BuChE, we review recent evidence that has extended knowledge into the roles of ChEs in health, disease and aging.
Keywords: acetylcholinesterase, butyrylcholinesterase, alzheimers disease, dementia, dementia with lewy bodies
Current Alzheimer Research
Title: Cholinesterases: Roles in the Brain During Health and Disease
Volume: 2 Issue: 3
Author(s): Clive G. Ballard, Nigel H. Greig, Angela L. Guillozet-Bongaarts, Albert Enz and Sultan Darvesh
Affiliation:
Keywords: acetylcholinesterase, butyrylcholinesterase, alzheimers disease, dementia, dementia with lewy bodies
Abstract: The cholinergic hypothesis of decline in dementia, whereby deficits in learning, memory and behavior are caused, at least in part, by decreased levels of acetylcholine (ACh) in the brain, first emerged more than 20 years ago. The role for acetylcholinesterase (AChE) and its inhibition in this scheme has long been accepted, but findings from preclinical experiments and clinical trials have placed butyrylcholinesterase (BuChE) alongside AChE as an important contributor to the occurrence, symptoms, progression and responses to treatment in dementia. A number of new lines of evidence suggest that both cholinesterase inhibitors (ChEs) may have broader functions in the CNS than previously thought, which relate to both classical esterase activities of the enzymes as well as non-classical actions unrelated to their enzymatic function. Data suggest involvement of the ChEs in modulating glial activation, cerebral blood flow, the amyloid cascade, and tau phosphorylation. It has therefore been speculated that some actions of the ChEs could affect the underlying disease processes in Alzheimers disease (AD), and that pharmacological manipulation with ChE inhibitors may affect longterm disease progression. Focusing on new findings relating to BuChE, we review recent evidence that has extended knowledge into the roles of ChEs in health, disease and aging.
Export Options
About this article
Cite this article as:
Ballard G. Clive, Greig H. Nigel, Guillozet-Bongaarts L. Angela, Enz Albert and Darvesh Sultan, Cholinesterases: Roles in the Brain During Health and Disease, Current Alzheimer Research 2005; 2 (3) . https://dx.doi.org/10.2174/1567205054367838
DOI https://dx.doi.org/10.2174/1567205054367838 |
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
-
The Estrogenic Burden on Vascular Risk in Male-to-Female Transsexuals
Current Pharmaceutical Design Triggering Receptor Expressed on Myeloid Cells (TREM) Family and the Application of Its Antagonists
Recent Patents on Anti-Infective Drug Discovery Brain Structural Effects of Antidepressant Treatment in Major Depression
Current Neuropharmacology Probing Cerebrovascular Alterations in Alzheimers Disease Using MRI: From Transgenic Models to Patients
Current Medical Imaging Memory Enhancing Effect of Black Pepper in the AlCl3 Induced Neurotoxicity Mouse Model is Mediated Through Its Active Component Chavicine
Current Pharmaceutical Biotechnology Social Network Analysis of Dementia Wards in Psychiatric Hospitals to Explore the Advancement of Personhood in Patients with Alzheimer’s Disease
Current Alzheimer Research Folic Acid Can Contribute to Memory Deficit and Na+, K+- ATPase Failure in the Hippocampus of Adolescent Rats Submitted to Hypoxia- Ischemia
CNS & Neurological Disorders - Drug Targets Targeting the PAC1 Receptor for Neurological and Metabolic Disorders
Current Topics in Medicinal Chemistry Possible Drug Candidates for Alzheimers Disease Deduced from Studying their Binding Interactions with α7 Nicotinic Acetylcholine Receptor
Medicinal Chemistry Microglial Activation and its Implications in the Brain Diseases
Current Medicinal Chemistry Pharmacogenetic Insights into Depression and Antidepressant Response: Does Sex Matter?
Current Pharmaceutical Design The Effects of Lipid-Regulating Therapy on Haemostatic Parameters
Current Pharmaceutical Design Coronary Artery Disease and Endothelial Dysfunction: Novel Diagnostic and Therapeutic Approaches
Current Medicinal Chemistry Ceruloplasmin, the Unique Multi-Copper Oxidase of Vertebrates
Protein & Peptide Letters An Antioxidant Role by Minocycline Via Enhancing the Activation of LKB1/AMPK Signaling in the Process of Cerebral Ischemia Injury
Current Molecular Medicine Current Developments of Coumarin Compounds in Medicinal Chemistry
Current Pharmaceutical Design Vitamin E - Occurrence, Biosynthesis by Plants and Functions in Human Nutrition
Mini-Reviews in Medicinal Chemistry Transgenic Overproduction of Omega-3 Polyunsaturated Fatty Acids Provides Neuroprotection and Enhances Endogenous Neurogenesis After Stroke
Current Molecular Medicine Biomarkers for Alzheimer’s Disease
Current Alzheimer Research Following Intracellular Cholesterol Transport by Linear and Non-Linear Optical Microscopy of Intrinsically Fluorescent Sterols
Current Pharmaceutical Biotechnology