Hicks_2013_J.Biol.Chem_288_26039

Reference

Title : The amyloid precursor protein represses expression of acetylcholinesterase in neuronal cell lines - Hicks_2013_J.Biol.Chem_288_26039
Author(s) : Hicks DA , Makova NZ , Gough M , Parkin ET , Nalivaeva NN , Turner AJ
Ref : Journal of Biological Chemistry , 288 :26039 , 2013
Abstract :

The toxic role of amyloid beta peptides in Alzheimer's disease is well documented. Their generation is via sequential beta- and gamma-secretase cleavage of the membrane-bound amyloid precursor protein (APP). Other APP metabolites include the soluble ectodomains sAPPalpha and sAPPbeta 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 gamma-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 beta 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 sAPPalpha, sAPPbeta, and AICD.

PubMedSearch : Hicks_2013_J.Biol.Chem_288_26039
PubMedID: 23897820

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Citations formats

Hicks DA, Makova NZ, Gough M, Parkin ET, Nalivaeva NN, Turner AJ (2013)
The amyloid precursor protein represses expression of acetylcholinesterase in neuronal cell lines
Journal of Biological Chemistry 288 :26039

Hicks DA, Makova NZ, Gough M, Parkin ET, Nalivaeva NN, Turner AJ (2013)
Journal of Biological Chemistry 288 :26039