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- W2090927731 startingPage "e87014" @default.
- W2090927731 abstract "Proteolytic processing of the amyloid precursor protein (APP) by the β- and γ-secretases releases the amyloid-β peptide (Aβ), which deposits in senile plaques and contributes to the etiology of Alzheimer's disease (AD). The α-secretase cleaves APP in the Aβ peptide sequence to generate soluble APPα (sAPPα). Upregulation of α-secretase activity through the 5-hydroxytryptamine 4 (5-HT4) receptor has been shown to reduce Aβ production, amyloid plaque load and to improve cognitive impairment in transgenic mouse models of AD. Consequently, activation of 5-HT4 receptors following agonist stimulation is considered to be a therapeutic strategy for AD treatment; however, the signaling cascade involved in 5-HT4 receptor-stimulated proteolysis of APP remains to be determined. Here we used chemical and siRNA inhibition to identify the proteins which mediate 5-HT4d receptor-stimulated α-secretase activity in the SH-SY5Y human neuronal cell line. We show that G protein and Src dependent activation of phospholipase C are required for α-secretase activity, while, unexpectedly, adenylyl cyclase and cAMP are not involved. Further elucidation of the signaling pathway indicates that inositol triphosphate phosphorylation and casein kinase 2 activation is also a prerequisite for α-secretase activity. Our findings provide a novel route to explore the treatment of AD through 5-HT4 receptor-induced α-secretase activation." @default.
- W2090927731 created "2016-06-24" @default.
- W2090927731 creator A5021772353 @default.
- W2090927731 creator A5057990599 @default.
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- W2090927731 creator A5079684147 @default.
- W2090927731 date "2014-01-21" @default.
- W2090927731 modified "2023-10-16" @default.
- W2090927731 title "Regulation of Amyloid Precursor Protein Processing by Serotonin Signaling" @default.
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- W2090927731 doi "https://doi.org/10.1371/journal.pone.0087014" @default.
- W2090927731 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3897773" @default.
- W2090927731 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24466315" @default.
- W2090927731 hasPublicationYear "2014" @default.
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