title: CTF1-51, a truncated carboxyl-terminal fragment of amyloid precursor protein, suppresses the effects of Aβ42-lowering γ-secretase modulators.
abstract: The pathogenesis of Alzheimer's disease (AD) is correlated with the toxicity of amyloid β-peptide (Aβ), especially Aβ42. γ-Secretase modulators (GSMs) are compounds that alter production of Aβ42 without interfering with the physiological function of γ-secretase. Aβ42-lowering GSMs have been studied with the hope of using them as therapeutic or prophylactic drugs for AD. However, the mechanism of action of GSMs is not well defined. We examined the effect of Aβ42-lowering GSMs on model cells producing large amounts of Aβ42: CHO cells expressing CTF1-51, a precursor peptide of Aβ that is mainly cleaved into Aβ42. Our results indicate that the effect of GSM in the model was weak. Thus, we conclude that CTF1-51 cleavage mainly yields Aβ42 and suppresses the effects of some GSMs, a phenomenon that may be related to their mechanism of action.
authors.affiliation: Department of Life Science, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Watahiki
authors.forename: Sosuke
authors.initials: S
authors.lastname: Yagishita
authors.forename: Eugene
authors.initials: E
authors.lastname: Futai
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ishiura
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D007052:Ibuprofen / Q000494:pharmacology*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D013467:Sulindac / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C078639:amyloid beta-protein (1-38); C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D013467:Sulindac; C025462:sulindac sulfide; D053829:Amyloid Precursor Protein Secretases; D007052:Ibuprofen