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22 février 2019: 1 événement

  • Département Biologie des Génomes

    Vendredi 22 février 11:00-12:00 - Frédéric Checler - Institut de Pharmacologie Moléculaire et Cellulaire, Sophia-Antipolis

    Presenilins-PINK1 functional interplay governs mitophagic response

    Résumé : The amyloid cascade hypothesis postulates that the overload of canonical Aß could be a key event in Alzheimer’s disease (AD) setting and progression. One of the histological stigmata consistently reported in AD brain consists in the alteration of mitochondrial physiology and dynamics. Such feature also stands in other neurodegenerative pathologies including Parkinson’s disease. However, little was known concerning the molecular mechanisms underlying these dysfunctions. We have recently delineated a functional interplay linking presenilins also referred to as -secretase, the enzyme responsible for the production of amyloid peptides that accumuate in AD-affected brains, and Pink-1, one of the proteins responsible for a subset of autosomal recessive cases of Parkinson’s disease (FPD). We show that this molecular dialogue drives mitophagic response. Further, we establish that parkin (another FPD-linked protein) acts upstream of Pink-1 to control its function in a PS-dependent manner. Overall, our studies established a novel function of PS that explains, at least in part, the mechanistic defects underlying mitochondrial dysfunctions observed in AD and confirmed our hypothesis of a molecular dialogue and functional interplay between proteins involved in distinct neurodegenerative pathologies.
    1- GOIRAN T., et al. (2018) Biological Psychiatry, 83, 416-427

    Lieu : Auditorium I2BC - Bâtiment 21, Campus de Gif-sur-Yvette

    En savoir plus : Département Biologie des Génomes