Abstract
Alzheimers disease (AD) is linked to cholinergic deficiency and the overactivation of glutamate receptors. The acetylcholinesterase (AChE) inhibition treatment approach has produced the most encouraging results in clinical practice, and memantine, a moderate antagonist of N-methyl-D-aspartate (NMDA) receptors, has been approved for treating AD. However, AChE inhibitors have limited success as they only improve memory in mild dementia but cannot stop the process of neurodegeneration; while memantine possesses neuroprotective effects only with a little ability in memory enhancement. There has been a major rush among neuroscience research institutions and pharmaceutical firms worldwide to search for safer and more effective therapeutic agents for AD. The novel dimers, derived from tacrine and the fragment of huperzine A (HA), have been demonstrated to be potent and selective reversible inhibitors of AChE. Bis(7)-tacrine, bis(12)-hupyridone (E12E) and HA(10)-tacrine, are representatives of three series of novel dimers. According to the preclinical studies, these compounds have been shown to have low toxicity and high efficacy for improving cognitive deficits in several animal models. More interestingly, bis(7)-tacrine, similar to memantine, prevents glutamate-induced neurotoxicity by moderately blocking glutamate receptor NMDA subtype. Furthermore, bis(7)-tacrine, as well as E12E, possesses multiple neuroprotective effects in vitro and in vivo. Taking together, these dimeric AChE inhibitors, especially bis(7)- tacrine, E12E and HA(10)-tacrine, may provide beneficial effects in AD and other neurodegenerative diseases.
Keywords: Alzheimer's disease, acetylcholinesterase inhibitor, dimers, bis(7)-tacrine, neuroprotection
Current Alzheimer Research
Title: East Meets West in the Search for Alzheimers Therapeutics - Novel Dimeric Inhibitors from Tacrine and Huperzine A
Volume: 4 Issue: 4
Author(s): W. M. Li, K. K.W. Kan, P. R. Carlier, Y. P. Pang and Y. F. Han
Affiliation:
Keywords: Alzheimer's disease, acetylcholinesterase inhibitor, dimers, bis(7)-tacrine, neuroprotection
Abstract: Alzheimers disease (AD) is linked to cholinergic deficiency and the overactivation of glutamate receptors. The acetylcholinesterase (AChE) inhibition treatment approach has produced the most encouraging results in clinical practice, and memantine, a moderate antagonist of N-methyl-D-aspartate (NMDA) receptors, has been approved for treating AD. However, AChE inhibitors have limited success as they only improve memory in mild dementia but cannot stop the process of neurodegeneration; while memantine possesses neuroprotective effects only with a little ability in memory enhancement. There has been a major rush among neuroscience research institutions and pharmaceutical firms worldwide to search for safer and more effective therapeutic agents for AD. The novel dimers, derived from tacrine and the fragment of huperzine A (HA), have been demonstrated to be potent and selective reversible inhibitors of AChE. Bis(7)-tacrine, bis(12)-hupyridone (E12E) and HA(10)-tacrine, are representatives of three series of novel dimers. According to the preclinical studies, these compounds have been shown to have low toxicity and high efficacy for improving cognitive deficits in several animal models. More interestingly, bis(7)-tacrine, similar to memantine, prevents glutamate-induced neurotoxicity by moderately blocking glutamate receptor NMDA subtype. Furthermore, bis(7)-tacrine, as well as E12E, possesses multiple neuroprotective effects in vitro and in vivo. Taking together, these dimeric AChE inhibitors, especially bis(7)- tacrine, E12E and HA(10)-tacrine, may provide beneficial effects in AD and other neurodegenerative diseases.
Export Options
About this article
Cite this article as:
Li M. W., Kan K.W. K., Carlier R. P., Pang P. Y. and Han F. Y., East Meets West in the Search for Alzheimers Therapeutics - Novel Dimeric Inhibitors from Tacrine and Huperzine A, Current Alzheimer Research 2007; 4 (4) . https://dx.doi.org/10.2174/156720507781788918
DOI https://dx.doi.org/10.2174/156720507781788918 |
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
-
Butyrylcholinesterase as a Diagnostic and Therapeutic Target for Alzheimer’s Disease
Current Alzheimer Research Data Tagging in Medical Images: A Survey of the State-of-Art
Current Medical Imaging Natural Product Formulations for the Prevention and Treatment of Alzheimer's disease: A Patent Review
Recent Patents on Drug Delivery & Formulation The Differential Diagnostic Value of the Callosal Angle and Evans Index in Mild Cognitive Impairment and Alzheimer's Disease
Current Medical Imaging Will Diverse Tat Interactions Lead to Novel Antiretroviral Drug Targets?
Current Drug Targets Recent Progress of Imaging Agents for Parkinson’s Disease
Current Neuropharmacology Experience and Perspectives of Caregivers of Spouse with Mild Cognitive Impairment
Current Alzheimer Research The Effect of Cyberspace-Based Education on the Well-Being of Caregivers of Elderly People with Dementia
Current Aging Science Ameliorative Effect of Trans-Sinapic Acid and its Protective Role in Cerebral Hypoxia in Aluminium Chloride Induced Dementia of Alzheimer's Type
CNS & Neurological Disorders - Drug Targets Non-Celiac Gluten Sensitivity Triggers Gut Dysbiosis, Neuroinflammation, Gut-Brain Axis Dysfunction, and Vulnerability for Dementia
CNS & Neurological Disorders - Drug Targets Molecular Chaperones as Rational Drug Targets for Parkinsons Disease Therapeutics
CNS & Neurological Disorders - Drug Targets The Blood-Brain Barrier: Its Influence in the Treatment of Brain Tumors Metastases
Current Cancer Drug Targets Toxics of Tobacco Smoke and Cardiovascular System: From Functional to Cellular Damage
Current Pharmaceutical Design Patent Selections
Recent Patents on Cardiovascular Drug Discovery Herbal Medicine for Slowing Aging and Aging-associated Conditions: Efficacy, Mechanisms and Safety
Current Vascular Pharmacology ADAM17 as a Therapeutic Target in Multiple Diseases
Current Pharmaceutical Design Cortical and Subcortical Changes in Alzheimer’s Disease: A Longitudinal and Quantitative MRI Study
Current Alzheimer Research Role of LXR and ABCA1 in the Pathogenesis of Alzheimers Disease -Implications for a New Therapeutic Approach
Current Alzheimer Research The Effects of Psychological Stress on Depression
Current Neuropharmacology Neuropathological Correlates of Cerebral Multimorbidity
Current Alzheimer Research