Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between European scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other.

The Netherlands
Towards the understanding of pathological protein processing and toxicity in Machado-Joseph Disease

Project Coordinator

Institute of Reconstructive Neurbiology University of Bonn


Daniel Kaganovich Department of Cell and Developmental Biology Hebrew University of Jerusalem Jerusalem Jerusalem, Israel
Dineke Verbeek Department of Genetics University of Groningen Groningen Groningen, The Netherlands
Luis Pereira de Almeida Center for Neurosciences and Cell Biology of Coimbra University of Coimbra Coimbra Coimbra, Portugal
Thorsten Schmidt Medical Genetics University of Tübingen Tübingen Tübingen, Germany

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.

E-Rare 2012 - Created by Toussaint Biger