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Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
Impaired PGC-1alpha function in muscle in Huntington's disease
Rajnish K Chaturvedi1, Peter Adhihetty, Shubha Shukla
1Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, NY 10065, USA. rajnish@iitr.res.in
Human Molecular Genetics
|May 23, 2009
Summary
Impaired PPAR gamma coactivator 1alpha (PGC-1alpha) function contributes to muscle dysfunction in Huntington's disease (HD). Enhancing PGC-1alpha may offer therapeutic benefits for HD patients.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Huntington's disease (HD) is a neurodegenerative disorder associated with muscle dysfunction.
- The role of PPAR gamma coactivator 1alpha (PGC-1alpha) in HD-related muscle pathology is not well understood.
Purpose of the Study:
- To investigate the role of PGC-1alpha in muscle dysfunction in HD.
- To explore therapeutic strategies targeting PGC-1alpha in HD.
Main Methods:
- Studied PGC-1alpha expression and function in HD transgenic mice and human HD muscle biopsies/myoblasts.
- Utilized beta-guanidinopropionic acid (GPA) to induce energy depletion and activate PGC-1alpha.
- Administered PGC-1alpha via adenoviral vectors in HD mice.
- Performed gene knockdown of mutant huntingtin.
Main Results:
- Reduced PGC-1alpha expression and target genes observed in HD mice and patients.
- GPA treatment improved muscle function in wild-type mice but not in HD mice.
- HD patient myoblasts showed reduced PGC-1alpha, oxidative fibers, and response to GPA.
- PGC-1alpha delivery reversed deficits in HD mice.
Conclusions:
- Impaired PGC-1alpha function is a critical factor in HD muscle dysfunction.
- Therapeutic strategies aimed at enhancing PGC-1alpha activity hold promise for HD treatment.
- Muscle tissue may serve as a valuable site for monitoring therapeutic interventions in HD.
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