Deregulation of the Ubiquitin-Proteasome System in Oculopharyngeal Muscular Dystrophy
Author Information
Author(s): Anvar Seyed Yahya, 't Hoen Peter AC, Venema Andrea, van der Sluijs Barbara, van Engelen Baziel, Snoeck Marc, Vissing John, Trollet Capucine, Dickson George, Chartier Aymeric, Simonelig Martine, van Ommen Gert-Jan B, van der Maarel Silvere M, Raz Vered
Primary Institution: Leiden University Medical Center
Hypothesis
OPMD-associated molecular mechanisms would be consistently deregulated across species.
Conclusion
The ubiquitin-proteasome system is the most consistently and significantly deregulated pathway in OPMD across species.
Supporting Evidence
- The ubiquitin-proteasome system was identified as the most significant and consistent OPMD-deregulated pathway across species.
- 80% of the OPMD-deregulated UPS genes show a progressive trend that is age-associated.
- Manipulations of proteasome activity specifically affect the accumulation and aggregation of mutant PABPN1.
- More than half of the OPMD-deregulated genes in Drosophila overlapped with their mouse or human homologous genes.
Takeaway
This study found that a system in our cells that helps break down proteins is not working properly in a muscle disease called OPMD, which affects how muscles function.
Methodology
An integrated high-throughput transcriptome study was performed in affected muscles of OPMD animal models and patients.
Limitations
Limited patient material due to OPMD being categorized as a rare disorder.
Participant Demographics
Higher prevalence reported in Jewish Caucasian and French-Canadian populations.
Statistical Information
P-Value
6.64E-08
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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