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2018-07-07 - Colloque/Présentation - communication orale - Anglais - 1 page(s)

Andre Séverine , Lecomte Marine, Muller Robert , Vander Elst Luce , Laurent Sophie , Burtea Carmen , "Phospholipase A2 targeting for the development of an original therapeutic strategy in the context of Alzheimer’s disease" in 11th FENS Forum of Neuroscience, Berlin, Germany, 2018

  • Codes CREF : Histologie (DI3212), Sciences biomédicales (DI3200), Biochimie pharmaceutique (DI3491), Biologie moléculaire (DI3111), Neuropathologie (DI332C), Chimie organique (DI1313), Biologie cellulaire (DI311D)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)
  • Centres UMONS : Centre de Recherche en Microscopie et Imagerie Médicale (CMMI)

Abstract(s) :

(Anglais) Alzheimer’s disease (AD), one of the main causes of dementia, is still incurable nowadays. The development of new therapeutic strategies for AD is thus a big challenge of scientific research. In this context, we developed an original complex of peptides, targeting an isoform of phospholipase A2 (PLA2) involved in this pathology, and being able to cross the blood-brain barrier. The inhibitory potential of this complex on PLA2 activity has been evaluated in vitro by the detection of arachidonic acid (AA) released from cells. The cellular localization of PLA2, COX2 and ALOX5 and the restructuration of actin cytoskeleton were studied by immunofluorescence. The benefit of this complex has been assessed in vivo on APP/PS1 mice by the evaluation of their spatial memory and the detection of amyloid plaques (AP) by immunohistochemistry. Our peptide complex can reduce the AA released by cells after PLA2 stimulation and is able to inhibit the translocation of PLA2, COX2 and ALOX5 to organelle membranes and plasma membrane processes following its binding to PLA2. It also showed to have effects on actin skeleton reorganization, phenomenon that contributes to glutamate excitotoxicity. In vivo, it seems to have beneficial effects on the spatial memory of APP/PS1 mice, revealed by the better results in the Barnes maze as compared to control mice. Moreover, treated mice exhibited a lower number of AP than those injected with a non-specific peptide. Taken together, these results reveal the potential of our complex to be an original therapeutic strategy in AD.


Mots-clés :
  • (Anglais) targeted delivery
  • (Anglais) therapy
  • (Anglais) peptides
  • (Anglais) LDLR
  • (Anglais) Alzheimer's disease
  • (Anglais) Phospholipase A2