title: Cholinesterase inhibition in Alzheimer's disease: is specificity the answer?
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.
authors.affiliation: Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Macdonald
authors.affiliation: Department of Medicine (Neurology and Geriatric Medicine), Dalhousie University, Halifax, NS, Canada.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rockwood
authors.affiliation: Department of Chemistry, Mount Saint Vincent University, Halifax, NS, Canada.
authors.forename: Earl
authors.initials: E
authors.lastname: Martin
authors.affiliation: 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.
authors.forename: Sultan
authors.initials: S
authors.lastname: Darvesh
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D006801:Humans
chemical_list: D014150:Antipsychotic Agents; D002800:Cholinesterase Inhibitors
keywords: (−) huperzine A; Acetylcholinesterase; bisnorcymserine; butyrylcholinesterase; donepezil; rivastigmine