Joint Transnational Call 2012 (JTC2012)
PPPT-MJD
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]