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Towards a unifying hypothesis of Alzheimer's disease: cholinergic system linked to plaques, tangles and neuroinflammation.

Authors
  • Sivaprakasam, Kannan1
  • 1 Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, 14853-2703, USA. [email protected]
Type
Published Article
Journal
Current medicinal chemistry
Publication Date
Jan 01, 2006
Volume
13
Issue
18
Pages
2179–2188
Identifiers
PMID: 16918347
Source
Medline
License
Unknown

Abstract

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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