2005
DOI: 10.2174/1567205054367838
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Cholinesterases: Roles in the Brain During Health and Disease

Abstract: The cholinergic hypothesis of decline in dementia, whereby deficits in learning, memory and behavior are caused, at least in part, by decreased levels of acetylcholine (ACh) in the brain, first emerged more than 20 years ago. The role for acetylcholinesterase (AChE) and its inhibition in this scheme has long been accepted, but findings from preclinical experiments and clinical trials have placed butyrylcholinesterase (BuChE) alongside AChE as an important contributor to the occurrence, symptoms, progression an… Show more

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Cited by 325 publications
(196 citation statements)
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“…The favorable effect was evident at well below what might be expected to represent a maximum tolerated dose, and the magnitude was similar to that of the AChE inhibitor, phenserine (29). Studies investigating genetic variants of BChE (the K-and atypicalvariants: BChE-K and -A) that are associated with a lowered innate ACh hydrolytic activity, suggest that links may exist between specific polymorphisms and AD pathology, but this remains controversial (41). Nevertheless, recent studies in humans support the potential role of BChE in cognition.…”
Section: Discussionmentioning
confidence: 90%
“…The favorable effect was evident at well below what might be expected to represent a maximum tolerated dose, and the magnitude was similar to that of the AChE inhibitor, phenserine (29). Studies investigating genetic variants of BChE (the K-and atypicalvariants: BChE-K and -A) that are associated with a lowered innate ACh hydrolytic activity, suggest that links may exist between specific polymorphisms and AD pathology, but this remains controversial (41). Nevertheless, recent studies in humans support the potential role of BChE in cognition.…”
Section: Discussionmentioning
confidence: 90%
“…18,23,26,27 Several lines of evidence indicate that butyrylcholinesterase (BuChE) has a significant role in cholinergic function, both in the normal brain and in AD. 29 Variation in the BuChE gene (BCHE) can lead to reduced activity of the enzyme. 30 The most common reported polymorphism is the K variant (BCHE-K).…”
Section: Introductionmentioning
confidence: 99%
“…50 Further investigation of the response to ChEI therapy across a range of AD severities associated with APOE and BCHE genotypes is warranted. 29 The objective of this study was to determine whether APOE or BCHE genotype predicts cognitive response to ChEI therapy.…”
Section: Introductionmentioning
confidence: 99%
“…Insight may derive from BuChE mutations in humans, that are not uncommon (Souza et al 2005), and several result in a loss of BuChE activity (akin to a steady-state level of inhibition). The BuChE-K variant (Ala539Thr) is present in some 33% of Caucasian and Asian individuals, and those possessing two alleles for BuChE-K (homozygous) show an approximate 30% reduced BuChE activity (Bartels et al 1992;Ballard et al 2005). In an increasing number of studies where AD subjects were genotyped for BuChE genetic variants and their disease progression measured (O'Brien et al 2003;Holmes et al 2005;Ballard et al 2005;Déniz-Naranjo et al 2007), those with BuChE deficiency had a delayed onset of AD and a slower cognitive decline compared to patients with wild-type BuChE levels.…”
Section: Discussionmentioning
confidence: 99%
“…The BuChE-K variant (Ala539Thr) is present in some 33% of Caucasian and Asian individuals, and those possessing two alleles for BuChE-K (homozygous) show an approximate 30% reduced BuChE activity (Bartels et al 1992;Ballard et al 2005). In an increasing number of studies where AD subjects were genotyped for BuChE genetic variants and their disease progression measured (O'Brien et al 2003;Holmes et al 2005;Ballard et al 2005;Déniz-Naranjo et al 2007), those with BuChE deficiency had a delayed onset of AD and a slower cognitive decline compared to patients with wild-type BuChE levels. The choice of which cymserine analogue to finally translate to clinical assessment will ultimately depend on the cost of bulk synthesis and tolerability in cellular and animal models.…”
Section: Discussionmentioning
confidence: 99%