en fr The role of the mitochondrial dysfunction in two neurodegenerative diseases, Huntingtons disease and Parkinsons disease Rôle de la dysfonction mitochondriale dans deux maladies neurodégénératives, la Maladie de HuntingtReport as inadecuate




en fr The role of the mitochondrial dysfunction in two neurodegenerative diseases, Huntingtons disease and Parkinsons disease Rôle de la dysfonction mitochondriale dans deux maladies neurodégénératives, la Maladie de Huntingt - Download this document for free, or read online. Document in PDF available to download.

1 CRICM - Centre de Recherche de l-Institut du Cerveau et de la Moelle épinière

Abstract : Mitochondrial dysfunction has been implicated in several neurodegenerative diseases and is correlated with augmented levels of intracellular oxydant stress. The mitochondrial defects observed in tissues from patients, as well as in animal and cellular models of Huntington’s and Parkinson’s diseases, suggest the implication of mitochondria in the pathogenesis of these diseases. The two projects discussed in this manuscript focus on the role of particular aspects of mitochondrial physiology in these diseases. By the first project we show the role of defective mitochondrial respiratory chain compex II in several rodent models of Huntington’s disease. By using a lentivirus-based gene transfert strategy we highlight the neuroprotective potential of the striatal overexpression of the subunits of complex II. The second project focus on Parkin and PINK1, two proteins implicated in the autosomal recessive, hereditary forms of Parkinson’s disease and in mitochondrial quality control mechanisms, such as mitophagy. In a cellular model we show that the two proteins facilitate Drp1-dependent mitochondrial fission. We show that Parkin may facilitate the signaling pathways controlling the activity of the pro-fission protein Drp1. This effect is probably indirect and mostly PINK1-independent. On the contrary, in mitochondrial depolarization conditions, by FRET Förster Resonance Energy Transfer a direct spatial coordination of Parkin, PINK1 and Drp1 is observed, which seems to be determinant for the efficiency of mitophagy. My projects shed new light on pathogenic mechanisms and open new perspectives in the research on these diseases.

Résumé : Un dysfonctionnement mitochondrial est impliqué dans plusieurs maladies neurodégénératives, corrélé avec une augmentation des niveaux de stress oxydant. Les anomalies mitochondriales observées dans les tissus des patients, les modèles animaux et cellulaires des maladies de Huntington et de Parkinson, suggèrent l-implication de la mitochondrie dans leur pathogénie.Les deux projets discutés dans ce manuscrit se focalisent sur le rôle des aspects particuliers de la physiologie mitochondriale au cours des deux maladies.

en fr

Keywords : Mitophagy Oxidant stress

Mots-clés : Mitophagie Fission Mitochondriale Chaîne respiratoire mitochondriale Transfert de genes Neurodégénérescence Stress Oxydant





Author: Maria Damiano -

Source: https://hal.archives-ouvertes.fr/



DOWNLOAD PDF




Related documents