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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

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 neuroinflammation

Paumier, 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.
2

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.
3

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 in print.
4

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.
5

Inhibition of membrane type 1-matrix metalloproteinase with mercaptosulfide inhibitors

Hurst, 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.
6

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.
7

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.
8

The expression of tissue inhibitor of metalloproteinase during the early stages of bone graft healing

Twitty, Anne. January 2000 (has links)
published_or_final_version / Dentistry / Doctoral / Doctor of Philosophy
9

An investigation of the plasminogen activator system and other oncoproteins in human bladder cancer

Dickinson, Andrew John January 1996 (has links)
No description available.
10

Regulation of metalloproteinase expression in vascular pathology

Kranzhöfer, Alexander Friedrich January 2002 (has links)
No description available.

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