Expression of APP, BACE1, AChE and ChAT in an AD model in rats and the effect of donepezil hydrochloride treatment

Li, Qiang; Chen, Min; Liu, Hong‐Min; Yang, Liqun; Yang, Guoqing

doi:10.3892/mmr.2012.1102

Cited by 21 publications

(15 citation statements)

References 30 publications

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“…Memory dysfunction is well known to be associated mainly with cholinergic neuron loss in several regions of the brain, especially the basal forebrain and hippocampal CA1 region [15,16,17]. Consistent with previous studies [18,19,20], ChAT (a specific marker for cholinergic cells) immunohistochemical results from this study indicated cholinergic neuron loss in the MS and hippocampal CA1 regions in AD-like mice.…”

Section: Resultssupporting

confidence: 91%

Neuroprotective Effects of Sulforaphane on Cholinergic Neurons in Mice with Alzheimer’s Disease-Like Lesions

Zhang

Fang

et al. 2014

IJMS

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Alzheimer’s disease (AD) is a common neurodegenerative disease in elderly individuals, and effective therapies are unavailable. This study was designed to investigate the neuroprotective effects of sulforaphane (an activator of NF-E2-related factor 2) on mice with AD-like lesions induced by combined administration of aluminum and d-galactose. Step-down-type passive avoidance tests showed sulforaphane ameliorated cognitive impairment in AD-like mice. Immunohistochemistry results indicated sulforaphane attenuated cholinergic neuron loss in the medial septal and hippocampal CA1 regions in AD-like mice. However, spectrophotometry revealed no significant difference in acetylcholine level or the activity of choline acetyltransferase or acetylcholinesterase in the cerebral cortex among groups of control and AD-like mice with and without sulforaphane treatment. Sulforaphane significantly increased the numbers of 5-bromo-2'-deoxyuridine-positive neurons in the subventricular and subgranular zones in AD-like mice which were significantly augmented compared with controls. Atomic absorption spectrometry revealed significantly lower aluminum levels in the brains of sulforaphane-treated AD-like mice than in those that did not receive sulforaphane treatment. In conclusion, sulforaphane ameliorates neurobehavioral deficits by reducing cholinergic neuron loss in the brains of AD-like mice, and the mechanism may be associated with neurogenesis and aluminum load reduction. These findings suggest that phytochemical sulforaphane has potential application in AD therapeutics.

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Section: Resultssupporting

confidence: 91%

Neuroprotective Effects of Sulforaphane on Cholinergic Neurons in Mice with Alzheimer’s Disease-Like Lesions

Zhang

Fang

et al. 2014

IJMS

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“…Choline acetyltransferase is encoded by the ChAT gene located on chromosome 10q 11.2 (Francis et al, 1999;Li et al, 2012). The ChAT rs2177369 polymorphism plays an important role in the formation of acetylcholine.…”

Section: Chatmentioning

confidence: 99%

Gene Polymorphisms Affecting the Pharmacokinetics and Pharmacodynamics of Donepezil Efficacy

Wang

Wan

et al. 2020

Front. Pharmacol.

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Donepezil (DNP) is the first-line drug used for Alzheimer's disease (AD). However, the therapeutic response rate of patients to DNP varies from 20 to 60%. The main reason for the large differences in the clinical efficacy of DNP therapy is genetic factors, some of which affect pharmacokinetics (PK), while others affect pharmacodynamics (PD). Thus, much emphasis has been placed on the investigation of an association between PK-and PD-related gene polymorphisms and therapeutic response to DNP, but a consistent view does not yet exist. In this review, we summarize recent findings regarding genetic factors influencing the clinical efficacy of DNP, including substantial differences in individual responses as a consequence of polymorphisms in Cytochrome P450 (CYP) 2D6, CY3A4, CY3A5, APOE, ABCA1, ABCB1, ESR1, BCHE, PON-1, CHRNA7, and CHAT. We also discuss possible strategies for the evaluation of the clinical efficacy of DNP, with a specific focus on possible biomarkers of PK/PD parameters, and provide perspectives and limitations within the field, which will also be beneficial for understanding the multiple mechanisms of DNP therapy in AD.

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“…The expression of APP cleaving enzymes is increased in the brain cortex of AD patients [ 41 ] and the mRNA expression of APP was also increased in AD rat models [ 42 ], and these effects are also associated with elevated brain A β concentrations [for review, see [ 43 ]]. It has been suggested that the activities of β - and γ -secretase enzymes are enhanced in the brains of AD individuals [ 33 , 44 ], which could elevate brain A β levels leading to formation of senile plaques (A β deposit) [for review, see [ 45 ]].…”

Section: Introductionmentioning

confidence: 99%

Neuroinflammatory Cytokines Induce Amyloid Beta Neurotoxicity through Modulating Amyloid Precursor Protein Levels/Metabolism

Alasmari

Alshammari

Alasmari

et al. 2018

BioMed Research International

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Neuroinflammation has been observed in association with neurodegenerative diseases including Alzheimer's disease (AD). In particular, a positive correlation has been documented between neuroinflammatory cytokine release and the progression of the AD, which suggests these cytokines are involved in AD pathophysiology. A histological hallmark of the AD is the presence of beta-amyloid (Aβ) plaques and tau neurofibrillary tangles. Beta-amyloid is generated by the sequential cleavage of beta (β) and gamma (γ) sites in the amyloid precursor protein (APP) by β- and γ-secretase enzymes and its accumulation can result from either a decreased Aβ clearance or increased metabolism of APP. Previous studies reported that neuroinflammatory cytokines reduce the efflux transport of Aβ, leading to elevated Aβ concentrations in the brain. However, less is known about the effects of neuroinflammatory mediators on APP expression and metabolism. In this article, we review the modulatory role of neuroinflammatory cytokines on APP expression and metabolism, including their effects on β- and γ-secretase enzymes.

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Expression of APP, BACE1, AChE and ChAT in an AD model in rats and the effect of donepezil hydrochloride treatment

Cited by 21 publications

References 30 publications

Neuroprotective Effects of Sulforaphane on Cholinergic Neurons in Mice with Alzheimer’s Disease-Like Lesions

Neuroprotective Effects of Sulforaphane on Cholinergic Neurons in Mice with Alzheimer’s Disease-Like Lesions

Gene Polymorphisms Affecting the Pharmacokinetics and Pharmacodynamics of Donepezil Efficacy

Neuroinflammatory Cytokines Induce Amyloid Beta Neurotoxicity through Modulating Amyloid Precursor Protein Levels/Metabolism

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