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2016-12-10 - Colloque/Présentation - poster - Anglais - 1 page(s)

Andre Séverine , Daldal Fatima, Delcroix Marie, Muller Robert , Vander Elst Luce , Laurent Sophie , Burtea Carmen , "Phospholipase A2 modulation in Alzheimer’s disease: new approach of treatment using peptides able to accede to the brain through the LDL receptor" in Joint meeting of the Belgian Neurological Society and Belgian Dementia Council (BeDeCo) December 10th 2016., Antwerp, University of Antwerp., Belgique, 2016

  • Codes CREF : Sciences biomédicales (DI3200)
  • 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) is one of the main causes of dementia and its treatment is a real challenge. Phospholipase A2 (PLA2) signaling pathway was recently revealed to be involved in this pathology [1], its modulation being already attempted in the treatment of neurological disorders [2]. In order to develop a new therapeutic strategy for the AD patients, we have identified a PLA2‐targeted peptide (PL‐P25) by phage display. PL‐P25 is able to prevent the PLA2 binding to cell membrane phospholipids and restores its activity in the range of controls. The preliminary in vitro tests have shown that H2O2‐induced human astrocytes (1321N1) and glutamateinduced mouse neurons (N18TG2) release lower levels of arachidonic acid when incubated with PL‐P25. On the other hand, the blood‐brain barrier (BBB) protects the brain against xenobiotics and limits the access of most molecules, including potential therapeutic agents. The development of non‐invasive BBB crossing strategies is thus crucial to accede to the central nervous system (CNS) without BBB disruption. Being an attractive shuttling strategy for drug delivery due to its involvement in LDL transcytosis [3], LDL receptor (LDLR) was targeted by phage display, allowing the identification of the peptide LR‐P2. This peptide colocalizes with LDLR on mouse brain slices and human brain endothelial cells (ACBRI376) and is endocytosed via a caveolae‐mediated non‐degradation pathway, whereas the lysosome degradation is bypassed. This peptide will be used as vector in order to facilitate the access to the brain of our therapeutic peptide described above.