Spelling suggestions: "subject:"metalloproteinase""
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Métalloprotéases matricielles et maladie d'Alzheimer : étude des rôles de MT1- et MT5-MMP dans l'amyloïdogenèse et la neuro-inflammation / Matrix metalloproteinases and Alzheimer's diseases : study of the roles of MT1- and MT5-MMP in amyloidogenesis and neuroinflammationPaumier, Jean-Michel 05 December 2018 (has links)
Au cours de mon doctorat, j’ai étudié le rôle des métalloprotéases MT1- et MT5-MMP dans la maladie d'Alzheimer (MA). In vivo, nos travaux montrent un effet bénéfique de la délétion en MT5-MMP chez le modèle murin 5xFAD de la MA qui se caractérise par : i) une diminution des taux de métabolites toxiques de l’APP, dont le C99 et l’Aβ ; ii) une réduction de la réponse inflammatoire avec des taux diminués de cytokines pro-inflammatoires ; iii) une préservation de l’intégrité des réseaux neuronaux, des activités synaptiques et des performances cognitives. In vitro, nous montrons que MT5-MMP interagit avec l’APP, accroît sa localisation dans les endosomes précoces - l’un des sièges importants de l’activité de BACE-1 (beta-site amyloid precursor protein cleaving enzyme 1) et de la γ-sécrétase - et augmente la libération d’Aβ. Après surexpression dans des cellules HEK (human embryonic kidney) exprimant de manière stable la mutation Swedish de l’APP (HEKSwe), nous montrons que MT1-MMP stimule la production de C99 et d’Aβ selon un processus dépendant de l'activité de BACE-1. MT1-MMP interagit avec l’APP et le clive en partenariat avec MMP-2 pour générer deux fragments aux propriétés inconnues. MT1-MMP, comme MT5-MMP, favorise le trafic de l’APP vers les endosomes, pouvant expliquer son potentiel pro-amyloïdogénique. Enfin, la surexpression d’une forme catalytiquement inactive de MT1-MMP n’induit aucun des effets observés avec la forme active de la protéase. L’ensemble de ces travaux permet d’envisager MT1- et MT5-MMP comme de nouvelles cibles thérapeutiques pour cibler à la fois les processus pro-amyloïdogéniques et pro-inflammatoires caractéristiques de la MA. / During my Ph.D., I studied the role of metalloproteinases MT1- and MT5-MMP in Alzheimer's disease (AD). In vivo, our work demonstrates a beneficial effect of the MT5-MMP deletion in the 5xFAD mouse model of AD, which is characterized by: i) a decrease in the levels of toxic metabolites of APP, including C99 and Aβ ; ii) a reduction in the inflammatory response with decreased levels of pro-inflammatory cytokines; iii) preservation of the integrity of neural networks, synaptic activities and cognitive performance. In vitro, we show that MT5-MMP interacts with APP, increases its localization in early endosomes - one of the important sites of BACE-1 (beta-site amyloid precursor protein cleaving enzyme 1) γ-secretase - and increases the release of Aβ. After overexpression in HEK (human embryonic kidney) cells stably expressing the Swedish APP mutation (HEKSwe), we show that MT1-MMP stimulates the production of C99 and Aβ according to a process dependent on BACE-1. Our data indicates that MT1-MMP interacts with the APP and cleaves it in partnership with MMP-2 to generate two fragments with unknown properties. MT1-MMP, like MT5-MMP, favors the trafficking of APP to early endosomes, which may explain its pro-amyloidogenic potential. Finally, overexpression of a catalytically inactive form of MT1-MMP induces none of the effects observed with the active form of the protease. All of this work makes it possible to consider MT1- and MT5-MMP as new therapeutic targets to target both pro-amyloidogenic and pro-inflammatory processes characteristic of AD.
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MT1-MMP regulates early lymphocyte development through notch signaling /Jin, Guoxiang. January 2009 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 177-205). Also available online.
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MT1-MMP regulates early lymphocyte development through notch signalingJin, Guoxiang. January 2009 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 177-205). Also available in print.
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Activation and regulation of protease-activated receptors /Ludeman, Matthew J. January 2005 (has links)
Thesis (Ph.D.)--University of California, San Francisco, 2005. / Includes bibliographical references. Also available online.
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Inhibition of membrane type 1-matrix metalloproteinase with mercaptosulfide inhibitorsHurst, Douglas R. Sang, Qing-Xiang Amy. January 2003 (has links)
Thesis (Ph. D.)--Florida State University, 2003. / Advisor: Dr. Qing-Xiang Amy Sang, Florida State University, College of Arts and Sciences, Dept. of Chemistry and Biochemistry. Title and description from dissertation home page (viewed Mar. 22, 2005). Includes bibliographical references.
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The role of metalloprotease-disintegrin (ADAM) proteins in postranslational processing of EGF receptor ligands and insights into regulatory mechanisms /Sahin, A. R. Umut. January 2005 (has links)
Thesis (Ph.D.)--Brown University, 2005. / Vita. Thesis advisor: Carl P. Blobel. Includes bibliographical references (leaves 91-101). Also available online.
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Systemic MMP inhibition augments wound repair in advanced periodontitis a controlled clinical trial : this thesis was submitted in fulfillment ... for the degree of Master of Science in Periodontics ... /Gapski, Ricardo Luis Das Neves. January 2003 (has links)
Thesis (M.S.)--University of Michigan, 2003. / Includes bibliographical references.
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The expression of tissue inhibitor of metalloproteinase during the early stages of bone graft healingTwitty, Anne. January 2000 (has links)
published_or_final_version / Dentistry / Doctoral / Doctor of Philosophy
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An investigation of the plasminogen activator system and other oncoproteins in human bladder cancerDickinson, Andrew John January 1996 (has links)
No description available.
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Regulation of metalloproteinase expression in vascular pathologyKranzhöfer, Alexander Friedrich January 2002 (has links)
No description available.
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