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

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Polyglutamine Disorders

Part of the book series: Advances in Experimental Medicine and Biology ((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.

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Authors and Affiliations

  1. Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal

    Clévio Nóbrega

  2. Centre for Biomedical Research, University of Algarve, Faro, Portugal

    Clévio Nóbrega

  3. Algarve Biomedical Center, University of Algarve, Faro, Portugal

    Clévio Nóbrega

  4. Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    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

  5. Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal

    Ana Vasconcelos-Ferreira, Janete Cunha-Santos, Cláudia Cavadas & Luís Pereira de Almeida

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  1. Clévio Nóbrega
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Correspondence to Clévio Nóbrega or Luís Pereira de Almeida .

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  1. Department of Biomedical Sciences and Medicine; Centre for Biomedical Research and Algarve Biomedical Center, University of Algarve, Faro, Portugal

    Clévio Nóbrega

  2. Center for Neuroscience and Cell Biology and Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal

    Luís Pereira de Almeida

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Nóbrega, C. et al. (2018). Molecular Mechanisms and Cellular Pathways Implicated in Machado-Joseph Disease Pathogenesis . In: Nóbrega, C., Pereira de Almeida, L. (eds) Polyglutamine Disorders. Advances in Experimental Medicine and Biology, vol 1049. Springer, Cham. https://doi.org/10.1007/978-3-319-71779-1_18

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