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Towards a Unifying Hypothesis of Alzheimer's Disease: Cholinergic System Linked to Plaques, Tangles and Neuroinflammation

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The central role of cholinergic system in Alzheimer's 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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Keywords: Alzheimer's disease; acetylcholinesterase inhibitors; amyloid plaque; cholinergic system; neurofibrillary tangles; neuroinflammation

Document Type: Research Article

Affiliations: Department of Molecular Biology and Genetics, 217 Biotechnology Building, Cornell University,Ithaca, NY, 14853-2703, USA.

Publication date: 2006-08-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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