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您的检索式：作者名="Alexandre Bourgeois"
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| 1 | Targeting γ-secretase triggers the selective enrichment of oligomeric APP-CTFs in brain extracellular vesicles from Alzheimer cell and mouse models显示文摘Background:We recently demonstrated an endolysosomal accumulation of theβ-secretase-derived APP C-terminal fragment(CTF)C99 in brains of Alzheimer disease(AD)mouse models.Moreover,we showed that the treatment with theγ-secretase inhibitor(D6)led to further increased endolysosomal APP-CTF levels,but also revealed extracellular APP-CTF-associated immunostaining.We here hypothesized that this latter staining could reflect extracellular vesicle(EV)-associated APP-CTFs and aimed to characterize theseγ-secretase inhibitor-induced APPCTFs.Methods:EVs were purified from cell media or mouse brains from vehicle-or D6-treated C99 or APPswedish expressing cells/mice and analyzed for APP-CTFs by immunoblot.Combined pharmacological,immunological and genetic approaches(presenilin invalidation and C99 dimerization mutants(GXXXG))were used to characterize vesicle-containing APP-CTFs.Subcellular APP-CTF localization was determined by immunocytochemistry.Results:Purified EVs from both AD cell or mouse models were enriched in APP-CTFs as compared to EVs from control cells/brains.Surprisingly,EVs from D6-treated cells not only displayed increased C99 and C99-derived C83 levels but also higher molecular weight(HMW)APP-CTF-immunoreactivities that were hardly detectable in whole cell extracts.Accordingly,the intracellular levels of HMW APP-CTFs were amplified by the exosomal inhibitor GW4869.By combined pharmacological,immunological and genetic approaches,we established that these HMW APP-CTFs correspond to oligomeric APP-CTFs composed of C99 and/or C83.Immunocytochemical analysis showed that monomers were localized mainly to the trans-Golgi network,whereas oligomers were confined to endosomes and lysosomes,thus providing an anatomical support for the selective recovery of HMW APP-CTFs in EVs.The D6-induced APP-CTF oligomerization and subcellular mislocalization was indeed due toγ-secretase blockade,since it similarly occurred in presenilin-deficient fibroblasts.Further,our data proposed that besides favoring APP-CTF oligomerization by preventing C99 proteolysis,γ-secretase inhibiton also led to a defective SorLA-mediated retrograde transport of HMW APP-CTFs from endosomal compartments to the TGN.Conclusions:This is the first study to demonstrate the presence of oligomeric APP-CTFs in AD mouse models,the levels of which are selectively enriched in endolysosomal compartments including exosomes and amplified byγ-secretase inhibition.Future studies should evaluate the putative contribution of these exosome-associated APP-CTFs in AD onset,progression and spreading. | Inger Lauritzen Anaïs Bécot Alexandre Bourgeois Raphaëlle Pardossi-Piquard Maria-Grazia Biferi Martine Barkats Fréderic Checler | 2019 | Translational Neurodegeneration2019，8，1： | 1 |
| 2 | Immune response to baculovirus expressed protein fragment amino acids 190 - 289 ofrespiratory syncytial virus (RSV) fusion protein 显示文摘 | Werle B Bourgeois C Alexandre A | 1998 | Vaccine1998，16，11： | 1 |
| 3 | PTH-independent regulation of blood calcium concentration by the calcium-sensing receptor显示文摘 | Loupy Alexandre Ramakrishnan Suresh Krishna Wootla Bharath Chambrey Régine de la Faille Renaud Bourgeois Soline Bruneval Patrick Mandet Chantal Christensen Erik Ilso Faure Hélène Cheval Lydie Laghmani Kamel Collet Corinne Eladari Dominique D | 2012 | EN2012，，9： | 1 |
| 4 | Immune response to baculovirus expressed protein fragment amino acids 190 -289 of respiratory syncytial virus (RSV) fusion protein 显示文摘 | Bettina Werle Catherine Bourgeois Anne Alexandre | 1998 | Vaccine1998，16，： | 1 |
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