Nicotinic Acetylcholine Receptor Agonists for the Treatment of Alzheimer's Dementia: An Update.

Autor: Hoskin JL; Barrow Neurological Institute, Phoenix, AZ., Al-Hasan Y; Barrow Neurological Institute, Phoenix, AZ., Sabbagh MN; Barrow Neurological Institute, Phoenix, AZ.; Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV.
Jazyk: angličtina
Zdroj: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco [Nicotine Tob Res] 2019 Feb 18; Vol. 21 (3), pp. 370-376.
DOI: 10.1093/ntr/nty116
Abstrakt: A significant portion of the clinical phenotype observed in Alzheimer's disease (AD) occurs through nicotinic acetylcholine receptors (nAChRs). Degeneration of cholinergic neurons, combined with aberrant nAChR expression and activation partially through amyloid-beta peptide (Aβ)-nAChR leads to upregulation of pro-inflammatory pathways and subsequently the progressive cognitive decline of AD. Interestingly, the cholinergic anti-inflammatory pathway is also mediated through nAChR particularly α7 nAChR. Thus, agonists of these receptors will likely exert pro-cognitive benefits through multiple mechanisms including stimulating the cholinergic pathway, modulating inflammation, and buffering the effects of amyloid. Despite this promising theoretical use, trials thus far have been complicated by adverse effects or minimal improvement. This review will provide an update on several pharmacological nAChR agonists tested in clinical trials and reasons that further investigation of nAChR agonists is merited.
Implications: nAChRs have consistently presented a promising theoretical use in the treatment of AD; however, trials thus far have been complicated by adverse effects or minimal improvement. This review will provide an update on several pharmacological nAChR agonists trialed and reasons that further investigation of nAChR agonists is merited.
(© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze: MEDLINE
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