Résumés
Résumé
La chorée de Huntington est une maladie neurodégénérative héréditaire dominante, caractérisée par l’apparition progressive d’une dyskinésie, de déficits cognitifs et de troubles émotionnels. Près d’une décennie après l’identification du gène et de la mutation responsable de cette maladie, celle-ci reste incurable. Néanmoins, le développement de modèles transgéniques a permis une avancée majeure dans la connaissance des mécanismes cellulaires et moléculaires précoces de la maladie. La mutation conduirait à un dérèglement de la transcription, à une altération de la dégradation des protéines défectueuses par les protéasomes, ainsi qu’à des processus excitotoxiques et à un dysfonctionnement des mitochondries. Cet article souligne les apports récents de l’utilisation de modèles transgéniques chez la souris et chez la drosophile dans la compréhension de la pathogénie et dans l’élaboration de nouvelles stratégies thérapeutiques.
Summary
Huntington’s disease is an hereditary dominant neurodegenerative disorder clinically characterised by progressive dyskinesia, cognitive decline and psychiatric disturbances. One decade after the identification of the gene whose mutation is responsible for the disease, this pathology remains incurable. However, major insights into early cellular and molecular basis of Huntington’s disease have arisen from transgenic models. Transcriptional dysregulation, abnormal degradation of misfolded proteins as well as excitotoxic processes and mitochondrial dysfunction are involved in Huntington’s disease. The present review discusses the recent insights gained from mouse and Drosophila models towards the understanding of pathogenesis and the development of new therapeutic tools.
Parties annexes
Références
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