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| 1 | Processing of the beta-amyloid precursor protein and its regulation in Alzheimer's disease显示文摘 | Checler F | 1995 | J Neurochem1995，65，4： | 1 |
| 2 | Processing of the beta-amyloid precursor protein and its regu- lation in Alzheimer's disease 显示文摘 | Checler F | 1995 | J Neurochem1995，65，4： | 1 |
| 3 | Amyloid precursor protein,presenilins,and alpha-Synuclein:molecular pathogenesis and pharmacological applications in Alzheimer′s disease显示文摘 | Suh YH Checler F | | 0，，03： | 1 |
| 4 | P53 in neurodegenerative diseases and brain cancers 显示文摘 | CHECLER F COSTA C A D | 2014 | Pharmacol Ther2014，142，1： | 1 |
| 5 | 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 |
| 6 | Amyloid precursor protein,presenilins,and -synuclein:molecular pathogenesis and pharmacological applications in Alzheimer's disease显示文摘 | Suh YH Checler F | | 0，，03： | 1 |
| 7 | Processing of the beta-amyloid precursor protein and its regulation in Alzheimer disease 显示文摘 | Checler F | 1995 | J Neurechem1995，65，4： | 1 |
| 8 | Alzheimer's disease: The amyloid cascade hypothesis-20 years on显示文摘 | Checler F Turner T | 2012 | Neurochem2012，120，1： | 1 |
| 9 | BACE1 is at the crossroad of a toxic vicious cycle involving cellular stress andβ-amyloid production in Alzheimer’s disease显示文摘 | Chami L Checler F | 2012 | Mol Neurodegener2012，7，1： | 1 |
| 10 | Alzheimer’s and prion diseases: distinctpathologies, common proteolytic denominators显示文摘 | Checler F Vincent B | 2002 | Trends Neurosci2002，25，61： | 1 |
| 11 | p53 in neurodegenerative diseases and brain cancers显示文摘 | Checler F Alves da Costa C | 2014 | Pharmacol Ther2014，142，1： | 1 |
| 12 | Combined pharmacological, mutational and cell biology approaches indicate that p53-dependent caspase 3 activation triggered by cellular prion is dependent on its endocytosis显示文摘 | Sunyach C Checler F | 2005 | J Neurochem2005，92，6： | 1 |
| 13 | Jurkat T cells express a functional neutral endopeptidase activity (CALLA) involved in T cell activation显示文摘 | Mari B Checler F Ponzio G | 1992 | EMBO J1992，11，11： | 1 |
| 14 | Wild-type but Not Parkinson's Disease-related Ala-53:Thr Mutantα-Synuclein Protects Neuronal Cells from Apoptotic Stimuli显示文摘 | Karine Ancolio Fre'de' ric Checler | 2000 | The Jounal of Biological Chemistry2000，275，24： | 1 |
| 15 | Amyloid precursor protein, presenilins, and α-Synuclein:molecular pathogenesis and pharmacological applications in Alzheimer's disease显示文摘 | Suh YH Checler F | 2002 | Pharmacol Rev2002，54，3： | 1 |
| 16 | Apoptosis in Parkinson/s disease: is p53 the missing link between genetic and sporadic Parkinsonism? 显示文摘 | Alves da Costa C Checler F | 2011 | Cell Siqnal2011，23，96： | 1 |
| 17 | APP epsilon,the esepsilon- secretase-derived N-terminal product of the beat-amyloid precursor protein, behaves as a type I protein and undergoes alpha-, beta-, and gamma-secretase cleavages显示文摘 | Lefranc-Jullien S Sunyach C Checler F | 2006 | J Neurochem2006，97，： | 1 |
| 18 | Apoptosis in Parkinson’s disease: Is p53 the missing link between genetic and sporadic Parkinsonism?显示文摘 | Cristine Alves da Costa Frédéric Checler | 2010 | Cellular Signalling2010，，： | 1 |
| 19 | P53 is regulated by and regulates members of the gamma-secretase com- plex 显示文摘 | Checler F Dunys J Alves da Costa C | 2010 | Neurodegener Dis2010，1，7： | 1 |
| 20 | Apoptosis in Parkinson's disease:is p53 the missing link between genetic and sporadic Parkinsonism显示文摘 | Alves da Costa C Checler F | | 0，，06： | 1 |
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