Abstract
The central role of cholinergic system in Alzheimers disease (AD) pathway is becoming increasingly significant as reports linking the various components of cholinergic neurotransmission with the other pathological hallmarks emerge. This review, while addressing the molecular mechanisms associated with the pathological hallmarks of the disease and their close interactions, also makes an attempt to address the critical question that evades an answer: Given the significant role played by cholinergic system in AD pathway, why do the cholinergic-mechanism-based drugs are not successful in reversing or arresting the disease progress? Further, as molecules of diverse structural features were shown to inhibit amyloid aggregation, an understanding of the generic pathway of amyloid aggregation slowly emerges. For the first time, a coherent view of amyloid aggregation is presented in this review. The possible role of neuroinflammatory response in the events leading to the degeneration of cholinergic neurons is also discussed.
Keywords: Alzheimer's disease, cholinergic system, amyloid plaque, neurofibrillary tangles, acetylcholinesterase inhibitors, neuroinflammation
Current Medicinal Chemistry
Title: Towards a Unifying Hypothesis of Alzheimers Disease: Cholinergic System Linked to Plaques, Tangles and Neuroinflammation
Volume: 13 Issue: 18
Author(s): Kannan Sivaprakasam
Affiliation:
Keywords: Alzheimer's disease, cholinergic system, amyloid plaque, neurofibrillary tangles, acetylcholinesterase inhibitors, neuroinflammation
Abstract: The central role of cholinergic system in Alzheimers disease (AD) pathway is becoming increasingly significant as reports linking the various components of cholinergic neurotransmission with the other pathological hallmarks emerge. This review, while addressing the molecular mechanisms associated with the pathological hallmarks of the disease and their close interactions, also makes an attempt to address the critical question that evades an answer: Given the significant role played by cholinergic system in AD pathway, why do the cholinergic-mechanism-based drugs are not successful in reversing or arresting the disease progress? Further, as molecules of diverse structural features were shown to inhibit amyloid aggregation, an understanding of the generic pathway of amyloid aggregation slowly emerges. For the first time, a coherent view of amyloid aggregation is presented in this review. The possible role of neuroinflammatory response in the events leading to the degeneration of cholinergic neurons is also discussed.
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Sivaprakasam Kannan, Towards a Unifying Hypothesis of Alzheimers Disease: Cholinergic System Linked to Plaques, Tangles and Neuroinflammation, Current Medicinal Chemistry 2006; 13 (18) . https://dx.doi.org/10.2174/092986706777935203
DOI https://dx.doi.org/10.2174/092986706777935203 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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