Machado-Joseph disease/spinocerebellar ataxia type 3

Handb Clin Neurol. 2012:103:437-49. doi: 10.1016/B978-0-444-51892-7.00027-9.


Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), may be the most common dominantly inherited ataxia in the world. Here I will review historical, clinical, neuropathological, genetic, and pathogenic features of MJD, and finish with a brief discussion of present, and possible future, treatment for this currently incurable disorder. Like many other dominantly inherited ataxias, MJD/SCA3 shows remarkable clinical heterogeneity, reflecting the underlying genetic defect: an unstable CAG trinucleotide repeat that varies in size among affected persons. This pathogenic repeat in MJD/SCA3 encodes an expanded tract of the amino acid glutamine in the disease protein, which is known as ataxin-3. MJD/SCA3 is one of nine identified polyglutamine neurodegenerative diseases which share features of pathogenesis centered on protein misfolding and accumulation. The specific properties of MJD/SCA3 and its disease protein are discussed in light of what is known about the entire class of polyglutamine diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Ataxin-3
  • Humans
  • Machado-Joseph Disease / etiology
  • Machado-Joseph Disease / genetics*
  • Machado-Joseph Disease / pathology
  • Nerve Tissue Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Proteostasis Deficiencies / complications
  • Repressor Proteins / genetics*


  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • ATXN3 protein, human
  • Ataxin-3