Abstract
Alzheimers disease (AD) is the most common form of neurodegenerative dementias worldwide. Amyloid-β deposition, neurofibrillary tangle formation and Neuroinflammation are the major pathogenetic mechanisms that in concert lead to memory dysfunction and decline of cognition. To date, there is no curative treatment for AD. Epidemiological analysis support the notion that sustained intake of non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk and delay the onset of AD. In contrast, therapeutic studies testing NSAID efficacy in AD patients have not yielded positive results. This suggests that either the investigated drugs have not addressed the mechanism of action required for mediating beneficial effects or that NSAIDs are effective at stages way before clinical onset of symptoms. The NSAIDs concerned are pleiotrophic in nature and interact with more than one pathomechanism. Therefore evidence for more than one neuroprotective action of NSAIDs has been put forward and it seems likely that some of the drugs act at multiple levels through more than one molecular mechanism. Some, even may not only be beneficial, but negative actions may be overruled by protective effects. Within these mechanisms, modulation of γ-secretase activity, the activation of the peroxisome proliferator- activated receptor-γ, binding to prostaglandin receptors or interactions at the blood-brain barrier may account for the observed protection from AD. This article reviews the current knowledge and views on the above mechanisms and critically discusses current obstacles and the potential as future AD therapeutics.
Keywords: Alzheimer's disease, amyloid-β, blood-brain barrier, transmembrane receptor, ABC transporter, clearance, nuclear hormone receptor, peroxisome proliferator activated receptor, nonsteroidal anti-inflammatory drug, γ-secretase modulation,
Current Alzheimer Research
Title: Molecular Mechanisms and Therapeutic Application of NSAIDs and Derived Compounds in Alzheimers Disease
Volume: 8 Issue: 2
Author(s): M. T. Heneka, M. P. Kummer, S. Weggen, B. Bulic, G. Multhaup, L. Munter, M. Hull, T. Pflanzner and C. U. Pietrzik
Affiliation:
Keywords: Alzheimer's disease, amyloid-β, blood-brain barrier, transmembrane receptor, ABC transporter, clearance, nuclear hormone receptor, peroxisome proliferator activated receptor, nonsteroidal anti-inflammatory drug, γ-secretase modulation,
Abstract: Alzheimers disease (AD) is the most common form of neurodegenerative dementias worldwide. Amyloid-β deposition, neurofibrillary tangle formation and Neuroinflammation are the major pathogenetic mechanisms that in concert lead to memory dysfunction and decline of cognition. To date, there is no curative treatment for AD. Epidemiological analysis support the notion that sustained intake of non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk and delay the onset of AD. In contrast, therapeutic studies testing NSAID efficacy in AD patients have not yielded positive results. This suggests that either the investigated drugs have not addressed the mechanism of action required for mediating beneficial effects or that NSAIDs are effective at stages way before clinical onset of symptoms. The NSAIDs concerned are pleiotrophic in nature and interact with more than one pathomechanism. Therefore evidence for more than one neuroprotective action of NSAIDs has been put forward and it seems likely that some of the drugs act at multiple levels through more than one molecular mechanism. Some, even may not only be beneficial, but negative actions may be overruled by protective effects. Within these mechanisms, modulation of γ-secretase activity, the activation of the peroxisome proliferator- activated receptor-γ, binding to prostaglandin receptors or interactions at the blood-brain barrier may account for the observed protection from AD. This article reviews the current knowledge and views on the above mechanisms and critically discusses current obstacles and the potential as future AD therapeutics.
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Cite this article as:
T. Heneka M., P. Kummer M., Weggen S., Bulic B., Multhaup G., Munter L., Hull M., Pflanzner T. and U. Pietrzik C., Molecular Mechanisms and Therapeutic Application of NSAIDs and Derived Compounds in Alzheimers Disease, Current Alzheimer Research 2011; 8 (2) . https://dx.doi.org/10.2174/156720511795256099
DOI https://dx.doi.org/10.2174/156720511795256099 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
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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
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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
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