A new therapeutic target in Alzheimer's disease treatment: Attention to butyryloholinesterase

N. H. Greig, T. Utsuki, Q. S. Yu, X. Zhu, H. W. Holloway, T. Perry, B. Lee, D. K. Ingram, D. K. Lahiri

Research output: Contribution to journalArticle

291 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly, characterised by widespread loss of central cholinergic function. The only symptomatic treatment proven effective to date is the use of cholinesterase (ChE) inhibitors to augment surviving cholinergic activity. ChE inhibitors act on the enzymes that hydrolyse acetylcholine (ACh) following synaptic release. In the healthy brain, acetylcholinesterase (AChE) predominates (80%) and butyrylcholinesterase (BuChE) is considered to play a minor role in regulating brain ACh levels. In the AD brain, BuChE activity rises while AChE activity remains unchanged or declines. Therefore both enzymes are likely to have involvement in regulating ACh levels and represent legitimate therapeutic targets to ameliorate the cholinergic deficit. The two enzymes differ in location, substrate specificity and kinetics. Recent evidence suggests that BuChE may also have a role in the aetiology and progression of AD beyond regulation of synaptic ACh levels. Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine, MF-8622) and ChE inhibitors such as rivastigmine, which have a dual inhibitory action on both AChE and BuChE, indicate potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias. The development of specific BuChE inhibitors and the continued use of ChE inhibitors with the ability to inhibit BuChE in addition to AChE should lead to improved clinical outcomes.

Original languageEnglish (US)
Pages (from-to)159-165
Number of pages7
JournalCurrent Medical Research and Opinion
Volume17
Issue number3
DOIs
StatePublished - Dec 1 2001

Fingerprint

Butyrylcholinesterase
Alzheimer Disease
Acetylcholinesterase
Cholinesterase Inhibitors
Acetylcholine
Cholinergic Agents
Rivastigmine
Therapeutics
Brain
Enzymes
Aptitude
Substrate Specificity
Neurodegenerative Diseases
Dementia

Keywords

  • Acetylcholinesterase
  • Alzheimer's disease
  • Amyloid
  • Butyrylcholinesterase
  • Cholinergic
  • Cognition
  • Inhibition

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A new therapeutic target in Alzheimer's disease treatment : Attention to butyryloholinesterase. / Greig, N. H.; Utsuki, T.; Yu, Q. S.; Zhu, X.; Holloway, H. W.; Perry, T.; Lee, B.; Ingram, D. K.; Lahiri, D. K.

In: Current Medical Research and Opinion, Vol. 17, No. 3, 01.12.2001, p. 159-165.

Research output: Contribution to journalArticle

Greig, NH, Utsuki, T, Yu, QS, Zhu, X, Holloway, HW, Perry, T, Lee, B, Ingram, DK & Lahiri, DK 2001, 'A new therapeutic target in Alzheimer's disease treatment: Attention to butyryloholinesterase', Current Medical Research and Opinion, vol. 17, no. 3, pp. 159-165. https://doi.org/10.1185/03007990152673800
Greig, N. H. ; Utsuki, T. ; Yu, Q. S. ; Zhu, X. ; Holloway, H. W. ; Perry, T. ; Lee, B. ; Ingram, D. K. ; Lahiri, D. K. / A new therapeutic target in Alzheimer's disease treatment : Attention to butyryloholinesterase. In: Current Medical Research and Opinion. 2001 ; Vol. 17, No. 3. pp. 159-165.
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