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Machado-Joseph disease/spinocerebellar ataxia type 3

Henry Paulson1

  • 1Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA. henryp@umich.edu

Handbook of Clinical Neurology
|August 11, 2011
PubMed

Insights

Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3 (SCA3), is a common inherited ataxia. This review covers its features and discusses current and future treatments for this incurable neurodegenerative disorder.

Area of Science:

  • Neurogenetics
  • Neuropathology
  • Molecular Neurology

Background:

  • Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is a prevalent dominantly inherited ataxia.
  • It is characterized by clinical heterogeneity stemming from an unstable CAG trinucleotide repeat expansion.
  • This expansion leads to an abnormal polyglutamine tract in the ataxin-3 protein.

Purpose of the Study:

  • To provide a comprehensive review of Machado-Joseph disease (MJD/SCA3).
  • To discuss historical, clinical, neuropathological, and genetic aspects.
  • To explore pathogenesis and potential therapeutic strategies for this incurable neurodegenerative disorder.

Main Methods:

  • Literature review of historical, clinical, neuropathological, and genetic studies on MJD/SCA3.
  • Analysis of pathogenic mechanisms related to polyglutamine diseases.
  • Discussion of current and future treatment options.

Main Results:

  • MJD/SCA3 exhibits significant clinical variability due to the size of the expanded CAG repeat.
  • The disease protein, ataxin-3, contains an expanded polyglutamine tract.
  • MJD/SCA3 shares pathogenic features with other polyglutamine neurodegenerative diseases, including protein misfolding and aggregation.

Conclusions:

  • Machado-Joseph disease (MJD/SCA3) is a complex neurodegenerative disorder with a genetic basis in expanded trinucleotide repeats.
  • Understanding its pathogenesis within the context of polyglutamine diseases is crucial.
  • Effective treatments remain a significant challenge, necessitating further research into present and future therapeutic avenues.

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