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Related Experiment Videos

Polyglutamine-containing proteins in schizophrenia.

R Joober1, C Benkelfat, M Jannatipour

  • 1Montréal General Hospital Research Institute and Center for Research in Neurosciences, Quebec, Canada.

Molecular Psychiatry
|March 24, 1999
PubMed
Summary
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Expanded polyglutamine tracts, linked to genetic anticipation, were found in some schizophrenia patients. These findings suggest a potential role for expanded polyglutamine proteins in schizophrenia pathogenesis.

Area of Science:

  • Neurogenetics
  • Molecular Psychiatry

Background:

  • Genetic anticipation, characterized by earlier disease onset and increased severity across generations, is observed in schizophrenia.
  • Unstable CAG repeat expansions are the molecular basis for anticipation in neurodegenerative diseases.
  • Enlarged CAG/CTG repeats are more common in schizophrenic patients than controls, suggesting a potential role in schizophrenia etiology.

Purpose of the Study:

  • To investigate the presence of polyglutamine-expanded tracts, encoded by CAG repeats, in proteins from schizophrenic patients.
  • To determine if expanded polyglutamine proteins are associated with schizophrenia.

Main Methods:

  • Proteins from schizophrenic patients (n=59) and controls (n=73) were analyzed using SDS-PAGE and Western blotting.
  • A monoclonal antibody (mab 1C2) specific for expanded polyglutamine arrays was used for detection.

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  • Proteins were probed for the presence of abnormal bands indicating expanded polyglutamine tracts.

    • Main Results:

    • Three abnormal protein bands (approx. 50 kDa) were detected in two unrelated schizophrenic patients and a sibling.
    • None of the normal controls exhibited these abnormal bands.
    • The presence of expanded polyglutamine-containing proteins was identified in a subset of schizophrenia cases.

    Conclusions:

    • Expanded polyglutamine-containing proteins, although rare, may contribute to the pathogenesis of schizophrenia.
    • These findings support the hypothesis that unstable CAG repeats play a role in schizophrenia.
    • Further research is warranted to elucidate the specific proteins and mechanisms involved.