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J Alzheimers Dis. 2014;42(2):379-84. doi: 10.3233/JAD-140219.

Cholinesterase inhibition in Alzheimer's disease: is specificity the answer?

Author information

1
Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada.
2
Department of Medicine (Neurology and Geriatric Medicine), Dalhousie University, Halifax, NS, Canada.
3
Department of Chemistry, Mount Saint Vincent University, Halifax, NS, Canada.
4
Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada Department of Medicine (Neurology and Geriatric Medicine), Dalhousie University, Halifax, NS, Canada Department of Chemistry, Mount Saint Vincent University, Halifax, NS, Canada.

Abstract

Cholinesterase inhibitors are the standard of care for Alzheimer's disease (AD). Acetylcholinesterase (AChE) catalyzes the hydrolysis of the cholinergic neurotransmitter acetylcholine. However, the related enzyme butyrylcholinesterase (BuChE) also breaks down acetylcholine and is likewise targeted by the same clinical cholinesterase inhibitors. The lack of clinical efficacy for the highly specific and potent AChE inhibitor, (-) huperzine A, is intriguing, given the known cholinergic deficit in AD. Based on the proven efficacy of inhibitors affecting both cholinesterases and the apparent failure of specific AChE inhibition, focused BuChE inhibition seems important for more effective treatment of AD. Therefore, BuChE-selective inhibitors provide promise for improved benefit.

KEYWORDS:

(−) huperzine A; Acetylcholinesterase; bisnorcymserine; butyrylcholinesterase; donepezil; rivastigmine

PMID:
24898642
DOI:
10.3233/JAD-140219
[Indexed for MEDLINE]

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