Joint Transnational Call 2012 (JTC2012)


Machado-Joseph Disease (MJD, syn. spinocerebellar ataxia type 3; SCA3) is a rare autosomal dominantly inherited neurodegenerative disorder with progressive cerebellar ataxia. It is caused by an increase of CAG trinucleotid repeats resulting in an expanded polyglutamine (polyQ) repeat of ataxin-3 (ATXN3). Compelling evidence indicates that the proteolytic cleavage of ATXN3 leads to the formation of misfolded intermediates, which eventually accumulate to form nuclear aggregates. However, the exact mechanism of how mutated ATXN3 leads to neurodegeneration remains elusive. The PPPT-MJD consortium will combine induced pluripotent stem cell technology with state-of-the-art neurogenetics, biochemical studies, imaging and animal models. Key focus of the consortium is the process of aggregation of ATXN3, mechanisms of intracellular transport, modes of degradation and the identification of novel disease modifying factors.

  • Koch, Philipp (Coordinator)
    Institute of Reconstructive Neurobiology University of Bonn [GERMANY]
  • Kaganovich, Daniel
    Department of Cell and Developmental Biology Hebrew University of Jerusalem [ISRAEL]
  • Verbeek, Dineke
    Department of Genetics University of Groningen [NETHERLANDS]
  • Pereira de Almeida, Luis
    Center for Neurosciences and Cell Biology University of Coimbra [PORTUGAL]
  • Schmidt, Thorsten
    Medical Genetics University of Tübingen [GERMANY]