The Team
  • Researchers

    Yvon TROTTIER

  • Post-Doctoral Fellows

    Anna NIEWIADOMSKA-CIMICKA

    Sweta SINGH

  • Phd Students

    Samantha CARRILLO-ROSAS

    Lorraine FIEVET

  • Engineers & Technicians

    Chantal WEBER

Translational medicine and neurogenetics

Polyglutamine expansion diseases: from pathomechanisms to therapeutic strategies

Polyglutamine (PolyQ) expansion diseases are a group of 9 adult-onset genetic disorders that result in progressive degeneration of brain areas specific to each disease. PolyQ diseases are caused by the expansion of unstable CAG trinucleotide repeats, which code for polyQ expansion in ubiquitously expressed disease proteins. Cognate wild type proteins bear a polymorphic polyQ, while expansion above a certain polyQ length threshold (around 35-40Q), confer toxic properties to mutant proteins. A correlation exists between polyQ length and disease severity: the larger the polyQ expansion, the more toxic is the mutant protein. There is yet no effective therapy to prevent or slow down pathogenic processes of these diseases.

Our laboratory is interested in unraveling the pathophysiological mechanisms of two polyQ diseases : Huntington’s Disease (HD) and SpinoCerebellar Ataxia 7 (SCA7). HD is the most frequent polyQ diseases with a prevalence of around 1 affected to 12 000 individuals. HD causes involuntary motor movements and cognitive decline, and results from the progressive degeneration of the striatum and some cortical layers. SCA7 is unique among polyQ diseases as it causes progressive retinal degeneration together with cerebellar atrophy, leading to blindness and ataxia. Comparison between these two diseases allows us to identify disease-specific and common pathomechnanisms.

Our objectives are : 1) to determine why expanded polyQ motifs are toxic by studying their structural and aggregation properties ; 2) to unravel the cellular and molecular mechanisms of toxicity in HD and SCA7; 3) to develop strategies to stimulate the clearance of toxic mutant proteins or to prevent toxic aggregation.

We address these fundamental and medical questions by combining biochemistry, biophysics, cell biology and « Omic » approaches, by analyzing cellular, mouse and zebrafish disease models and by using these models to develop therapeutic strategies.

Imprimer Envoyer

Université de Strasbourg
INSERM
CNRS

IGBMC - CNRS UMR 7104 - Inserm U 964
1 rue Laurent Fries / BP 10142 / 67404 Illkirch CEDEX / France Tél +33 (0)3 88 65 32 00 / Fax +33 (0)3 88 65 32 01 / directeur.igbmc@igbmc.fr