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Complex I defect in muscle from patients with Huntington's disease
J Arenas1, Y Campos, R Ribacoba
1Centro de Investigación and Unidad de Neuropatología, Hospital 12 de Octubre, Madrid, Spain.
Annals of Neurology
|March 20, 1998
Summary
Huntington's disease (HD) is linked to mitochondrial complex I defects in muscles, with severity correlating to CAG repeat expansion. Muscle changes and mitochondrial DNA deletions were also observed, suggesting energy deficits in HD patients.
Area of Science:
- Biochemistry
- Neuroscience
- Genetics
Background:
- Huntington's disease (HD) is a neurodegenerative disorder.
- Mitochondrial dysfunction is implicated in various neurodegenerative diseases.
Purpose of the Study:
- To investigate mitochondrial respiratory chain complex I function in muscle tissue of HD patients.
- To correlate the severity of complex I defects with clinical and genetic features of HD.
Main Methods:
- Muscle biopsy analysis
- Assessment of mitochondrial respiratory chain complex I activity
- Polymerase chain reaction (PCR) for mitochondrial DNA deletions
- Histopathological examination of muscle morphology
Main Results:
- Variable defects in mitochondrial complex I activity (25-63% of control) were found in HD patient muscle.
- The most severe complex I defect correlated with the greatest CAG triplet expansion.
- Muscle pathology revealed myopathic changes, including moth-eaten fibers and enlarged mitochondria.
- Multiple mitochondrial DNA deletions were detected in the patient with the most severe complex I defect.
Conclusions:
- Mitochondrial complex I defects are present in the muscle of HD patients.
- These findings support the role of energetic impairment and oxidative damage in the muscle pathology of Huntington's disease.