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Updated: Jul 6, 2026

A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis
Published on: May 22, 2018
Distinct functional effects of human 5-HT4 receptor isoforms on beta-amyloid secretion
Sylvain J Robert1, Frank Lezoualc'h
1INSERM, U769 and IFR141, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France.
Background:
The serotonin 5-HT(4) receptor is of potential interest for the treatment of Alzheimer's disease because it increases memory and learning and influences amyloid precursor protein (APP) processing. Several 5-HT(4) receptor isoforms have been cloned in humans. They all belong to the G-protein-coupled receptor superfamily and differ in composition and length of their amino acid intracellular C-terminal sequence. At present, it is still unknown whether 5-HT(4) receptor isoforms may have distinct effects on APP processing.
Objective:
In this study, we investigated the effect of an ultrashort isoform of the human 5-HT(4) receptor (2 amino acids after the splicing site), the 5-HT(4(d)) receptor isoform (h5-HT(4(d))), on APP processing in Chinese hamster ovary cells (CHO cells).
Methods:
Non-amyloidogenic soluble sAPPalpha was determined by immunoblot and beta-amyloid peptides (Abeta(1-40) and Abeta(1-42)) were assayed by ELISA in CHO cells stably expressing h5-HT(4(d)) and transiently transfected with human APP(695).
Results:
We show here that activation of h5-HT(4(d)) strongly stimulates the release of sAPPalpha and concomitantly decreases extracellular Abeta peptides. These data contrast with our previous findings showing that the h5-HT(4(e/g)) receptor isoform, which has 20 amino acids after the splicing site, did not influence Abeta secretion.
Conclusion:
We conclude that C-terminal tails of 5-HT(4) receptor isoforms may influence their functional effect on Abeta secretion and that the pathways regulating either beta- or gamma-secretase may be differentially controlled by 5-HT(4) receptor isoforms.
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