title: Gamma-secretase inhibitor activity of a Pterocarpus erinaceus extract.
abstract: BACKGROUND
  Accumulation of β-amyloid peptides (Aβ) and its progressive deposition into amyloid plaques are key events in the aetiology of Alzheimer's disease (AD). To date, AD treatment is symptomatic and consists of drugs treating the cognitive decline.
  
  
  OBJECTIVE
  Identifying molecules specifically targeting Aβ production or aggregation represents a huge challenge in the development of specific AD treatments. Several molecules reported as γ-secretase inhibitors or modulators have been evaluated, but so far none of them have proven to be selective or fully efficient. We have previously investigated the potential interest of plant extracts and we reported that Pterocarpus erinaceus stem-bark extract was active on Aβ release. Our aim here was to characterize the mechanisms by which this extract reduces Aβ levels.
  
  
  METHODS
  We tested P. erinaceus extract at non-toxic concentrations on cells expressing the human amyloid precursor protein (APP695) or its amyloidogenic β-cleaved C-terminal fragment (C99), as well as on neuronal cell lines. P. erinaceus extract was found to inhibit Aβ release. We further showed that this extract inhibited γ-secretase activity in cell-free and in vitro assays, strongly suggesting that P. erinaceus extract is a natural γ-secretase inhibitor. Importantly, this extract did not inhibit γ-secretase-dependent Notch intracellular domain release.
  
  
  CONCLUSIONS
  P. erinaceus extract appears as a new potent γ-secretase inhibitor selective towards APP processing.
authors.affiliation: Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Salim
authors.initials: S
authors.lastname: Hage
authors.forename: Claudia
authors.initials: C
authors.lastname: Marinangeli
authors.forename: Serena
authors.initials: S
authors.lastname: Stanga
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Octave
authors.forename: Joëlle
authors.initials: J
authors.lastname: Quetin-Leclercq
authors.forename: Pascal
authors.initials: P
authors.lastname: Kienlen-Campard
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016564:Amyloid beta-Protein Precursor / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D035721:Pterocarpus; D014162:Transfection
chemical_list: D016564:Amyloid beta-Protein Precursor; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D053829:Amyloid Precursor Protein Secretases