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

Machado-Joseph disease/spinocerebellar ataxia type 3

Henry Paulson  1
Affiliations
Review

Machado-Joseph disease/spinocerebellar ataxia type 3

Henry Paulson. Handb Clin Neurol. 2012.

Abstract

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.

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Figures

Figure 1
Figure 1. Ataxin-3 and related Josephin domain proteins
Ataxin-3 is a relatively small protein with a glutamine repeat near the carboxyl terminus. The approximate ranges for normal and disease repeats are shown. The N-terminal conserved “josephin” catalytic domain, a predicted coiled-coil domain and several ubiquitin interacting motifs (UIMs) are also shown. Ataxin-3 is one member of the small Josephin DUB family, two other members of which are josephin-1 and josephin-2, encoded by different genes. All three proteins share the catalytic amino acid triad (C, H, and D/N) and function as DUBs.
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References

    1. Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S. Inclusion body formation reduces levels of mutant huntington and the risk of neuronal death. Nature. 2004;431:805–810. - PubMed
    1. Bence NF, Sampat RM, Kopito RR. Impairment of the ubiquitin-proteasome system by protein aggregation. Science. 2001;292:1552–5. - PubMed
    1. Berke SJ, Chai Y, Marrs GL, Wen H, Paulson HL. Defining the role of ubiquitin-interacting motifs in the polyglutamine disease protein, ataxin-3. J Biol Chem. 2005;280(36):32026–34. Epub 2005 Jul 21. - PubMed
    1. Berke SJ, Schmied FA, Brunt ER, Ellerby LM, Paulson HL. Caspase-mediated proteolysis of the polyglutamine disease protein ataxin-3. J. Neurochem. 2004 May;89(4):908–18. - PubMed
    1. Bevivino AE, Loll PJ. An expanded glutamine repeat destabilizes native ataxin-3 structure and mediates formation of parallel beta -fibrils. Proc Natl Acad Sci U S A. 2001;98:11955–60. - PMC - PubMed

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