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Cited by 654Cholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

The DOI matches its Crossref record; 206 of the 206 references it cites were found in a registry or an index.

Targeting acetylcholinesterase and butyrylcholinesterase in dementia

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Lane, Roger M., Potkin, Steven G., Enz, Albert·2005·The International Journal of Neuropsychopharmacology
DOI 10.1017/s1461145705005833
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Abstract

The cholinesterase inhibitors (ChE-Is) attenuate the cholinergic deficit underlying the cognitive and neuropsychiatric dysfunctions in patients with AD. Inhibition of brain acetylcholinesterase (AChE) has been the major therapeutic target of ChE-I treatment strategies for Alzheimer's disease (AD). AChE-positive neurons project diffusely to the cortex, modulating cortical processing and responses to new and relevant stimuli. Butyrylcholinesterase (BuChE)-positive neurons project specifically to the frontal cortex, and may have roles in attention, executive function, emotional memory and behaviour. Furthermore, BuChE activity progressively increases as the severity of dementia advances, while AChE activity declines. Therefore, inhibition of BuChE may provide additional benefits. The two cholinesterase (ChE) enzymes that metabolize acetylcholine (ACh) differ significantly in substrate specificity, enzyme kinetics, expression and activity in different brain regions, and complexity of gene regulation. In addition, recent evidence suggests that AChE and BuChE may have roles beyond 'classical' co-regulatory esterase functions in terminating ACh-mediated neurotransmission. 'Non-classical' roles in modulating the activity of other proteins, regional cerebral blood flow, tau phosphorylation, and the amyloid cascade may affect rates of AD progression. If these additional mechanisms are demonstrated to underlie clinically meaningful effects, modification of the over-simplistic cholinergic hypothesis in AD that is limited to symptomatic treatment, ignoring the potential of cholinergic therapies to modify the disease process, may be appropriate. The specificity of ChE inhibitory activity, up-regulation of AChE activity and changes in the composition of AChE molecular forms over time, selectivity for AD-relevant ChE molecular forms, brain vs. peripheral selectivity, and pharmacokinetic profile may be important determinants of the acute and long-term efficacy, safety and tolerability profiles of the different ChE-Is. This review focuses on new evidence for the roles of BuChE and AChE in symptom generation and rate of underlying disease progression in dementia, and argues that it may be appropriate to re-evaluate the place of ChE-Is in the treatment of dementia.

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Research works printed but not linked: 17

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Metadata

Authors
Lane, R. M., Potkin, S. G., & Enz, A.
Affiliations
  • Novartis (United States) (US)
  • University of California, Irvine (US)
  • Novartis (Switzerland) (CH)
Corresponding author
Potkin, Steven G.
ORCID
Venue
The International Journal of Neuropsychopharmacology
Publisher
Oxford University Press (OUP)
Published
2005-08-05
Volume
9
Issue
01
Pages
101
ISSN
  • 1461-1457 (ISSN-L)
  • 1469-5111
DOI
10.1017/s1461145705005833
OpenAlex
W2158603760
Cited by
654
References
206
Citations by year
2026: 43 · 2025: 37 · 2024: 47 · 2023: 40 · 2022: 54 · 2021: 45 · 2020: 47 · 2019: 46 · 2018: 41 · 2017: 26 · 2016: 36 · 2015: 25 · 2014: 30 · 2013: 20 · 2012: 25
FWCI
1.62
Type
journal article
Language
en
Open access
Locations
  • The International Journal of Neuropsychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
acetylcholinesterase, butyrylcholinesterase, cholinesterase inhibitors, Alzheimer's disease, dementia, cholinergic hypothesis, acetylcholine, frontal cortex, tau phosphorylation, amyloid hypothesis, disease progression, neuropsychiatric symptoms, enzyme substrate specificity
MeSH terms
Acetylcholinesterase, Alzheimer Disease, Animals, Butyrylcholinesterase, Central Nervous System, Cerebrovascular Circulation, Cholinergic Fibers, Cholinesterase Inhibitors, Dementia, Gene Expression Regulation, Humans, Isoenzymes, Neuroglia, Polymorphism, Genetic, Drug Delivery Systems

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