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• W1964076310 endingPage "26051" @default.
• W1964076310 startingPage "26039" @default.
• W1964076310 abstract "The toxic role of amyloid β peptides in Alzheimer's disease is well documented. Their generation is via sequential β- and γ-secretase cleavage of the membrane-bound amyloid precursor protein (APP). Other APP metabolites include the soluble ectodomains sAPPα and sAPPβ and also the amyloid precursor protein intracellular domain (AICD). In this study, we examined whether APP is involved in the regulation of acetylcholinesterase (AChE), which is a key protein of the cholinergic system and has been shown to accelerate amyloid fibril formation and increase their toxicity. Overexpression of the neuronal specific isoform, APP695, in the neuronal cell lines SN56 and SH-SY5Y substantially decreased levels of AChE mRNA, protein, and catalytic activity. Although similar decreases in mRNA levels were observed of the proline-rich anchor of AChE, PRiMA, no changes were seen in mRNA levels of the related enzyme, butyryl-cholinesterase, nor of the high-affinity choline transporter. A γ-secretase inhibitor did not affect AChE transcript levels or enzyme activity in SN56 (APP695) or SH-SY5Y (APP695) cells, showing that regulation of AChE by APP does not require the generation of AICD or amyloid β peptide. Treatment of wild-type SN56 cells with siRNA targeting APP resulted in a significant up-regulation in AChE mRNA levels. Mutagenesis studies suggest that the observed transcriptional repression of AChE is mediated by the E1 region of APP, specifically its copper-binding domain, but not the C-terminal YENTPY motif. In conclusion, AChE is regulated in two neuronal cell lines by APP in a manner independent of the generation of sAPPα, sAPPβ, and AICD." @default.
• W1964076310 created "2016-06-24" @default.
• W1964076310 creator A5042627723 @default.
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• W1964076310 creator A5061931209 @default.
• W1964076310 creator A5082657076 @default.
• W1964076310 creator A5090483862 @default.
• W1964076310 date "2013-09-01" @default.
• W1964076310 modified "2023-10-15" @default.
• W1964076310 title "The Amyloid Precursor Protein Represses Expression of Acetylcholinesterase in Neuronal Cell Lines" @default.
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• W1964076310 doi "https://doi.org/10.1074/jbc.m113.461269" @default.
• W1964076310 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3764808" @default.
• W1964076310 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23897820" @default.
• W1964076310 hasPublicationYear "2013" @default.
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