Affiliations: [a] Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada | [b] Department of Medicine (Neurology and Geriatric Medicine), Dalhousie University, Halifax, NS, Canada | [c] Department of Chemistry, Mount Saint Vincent University, Halifax, NS, Canada
Correspondence:
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Correspondence to: Sultan Darvesh, Room 1308, Camp Hill Veterans' Memorial Building 1, 5955 Veterans' Memorial Lane, Halifax, NS, B3H 2E1, Canada. Tel.: +1 902 473 2490; Fax: +1 902 473 7133; E-mail: [email protected].
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: Acetylcholinesterase, bisnorcymserine, butyrylcholinesterase, donepezil, (−) huperzine A, rivastigmine
