Quercetin stimulates the non-amyloidogenic pathway via activation of ADAM10 and ADAM17 gene expression in aluminum chloride-induced Alzheimer's disease rat model
2021
Elfiky, Asmaa M. | Mahmoud, Asmaa A. | Elreedy, Hala A. | Ibrahim, Khadiga S. | Ghazy, Mohamed A.
Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder characterized by declined cognitive functions in the elderly. Quercetin (Q) is a potent flavonol that has neuroprotective effects on AD derangements. The present study aimed to evaluate the α-secretase stimulatory function of Q through activation of ADAM10 and ADAM17 gene expression in the aluminum chloride (AlCl3)-induced AD rat model.After induction of AD in rats by oral administration of AlCl3 (50 mg/kg) for 28 days, the Q doses (25 and 50 mg/kg) were orally administered for 28 days. Rats performed the behavioral assessments during the last week of the treatment period. Hippocampi were harvested for assessments of the neurochemical and histopathological examinations and gene expression analysis.Administration of Q to AlCl₃-induced AD rat model attenuated behavioral deficits, improved cholinergic and dopaminergic dysfunctions, and diminished insoluble amyloid β (Aβ) plaques aggregation in the hippocampus. These ameliorative effects of Q were associated with down-regulation of APP, BACE1, APH1, and PSEN1 and up-regulation of ADAM10 and ADAM17 gene expression levels in the hippocampus.The present study suggests that Q might attenuate neurotransmission impairment, Aβ aggregation in the hippocampus, and behavioral deficits in the AlCl₃-induce AD rat model via up-regulating ADAM 10 and ADAM 17 (α-secretase) gene expression, leading to the inhibition of the amyloidogenic pathway. In support of the present finding, we suggest that ADAM10 and ADAM17 activation might be potential drug targets for AD to counteract the Aβ aggregation and cognitive deterioration.
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