Molecular Mechanisms and Cellular Pathways Implicated in Machado-Joseph Disease Pathogenesis

  • Clévio Nóbrega
  • Ana Teresa Simões
  • Joana Duarte-Neves
  • Sónia Duarte
  • Ana Vasconcelos-Ferreira
  • Janete Cunha-Santos
  • Dina Pereira
  • Magda Santana
  • Cláudia Cavadas
  • Luís Pereira de Almeida
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1049)

Abstract

Machado-Joseph disease (MJD) is a dominantly inherited disorder originally described in people of Portuguese descent, and associated with the expansion of a CAG tract in the coding region of the causative gene MJD1/ATX3. The CAG repeats range from 10 to 51 in the normal population and from 55 to 87 in SCA3/MJD patients. MJD1 encodes ataxin-3, a protein whose physiological function has been linked to ubiquitin-mediated proteolysis. Despite the identification of the causative mutation, the pathogenic process leading to the neurodegeneration observed in the disease is not yet completely understood. In the past years, several studies identified different molecular mechanisms and cellular pathways as being impaired or deregulated in MJD. Autophagy, proteolysis or post-translational modifications, among other processes, were implicated in MJD pathogenesis. From these studies it was possible to identify new targets for therapeutic intervention, which in some cases proved successful in models of disease.

Keywords

Pathogenesis Molecular mechanisms Machado-Joseph disease 

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Clévio Nóbrega
    • 1
    • 2
    • 3
    • 4
  • Ana Teresa Simões
    • 4
  • Joana Duarte-Neves
    • 4
  • Sónia Duarte
    • 4
  • Ana Vasconcelos-Ferreira
    • 4
    • 5
  • Janete Cunha-Santos
    • 4
    • 5
  • Dina Pereira
    • 4
  • Magda Santana
    • 4
  • Cláudia Cavadas
    • 4
    • 5
  • Luís Pereira de Almeida
    • 4
    • 5
  1. 1.Department of Biomedical Sciences and MedicineUniversity of AlgarveFaroPortugal
  2. 2.Centre for Biomedical Research, University of AlgarveFaroPortugal
  3. 3.Algarve Biomedical Center, University of AlgarveFaroPortugal
  4. 4.Center for Neuroscience and Cell Biology, University of CoimbraCoimbraPortugal
  5. 5.Faculty of PharmacyUniversity of CoimbraCoimbraPortugal

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