Skeletal muscle-specific deficiency of Rab geranylgeranyl transferase beta subunit induces myopathy and exacerbates the symptoms caused by HMG-CoA reductase deficiency in mice - PubMed
4 hours ago
- #myopathy
- #RabGGT-β
- #HMG-CoA reductase
- Statins inhibit HMG-CoA reductase, which can cause myopathy, potentially due to reduced geranylgeranyl pyrophosphate (GGPP) in the mevalonate pathway.
- Researchers used muscle-specific knockout mouse models to study the roles of GGPP and RabGGT-β in myopathy, including Hmgcr, Rabggtb, and combined deficiencies.
- Hmgcr knockout led to myopathy, with early loss of mitochondria-rich muscle fibers, reversible by GGOH, indicating GGPP depletion drives the condition.
- Rabggtb knockout alone caused milder, delayed myopathy, but combined with Hmgcr deficiency, it accelerated and worsened symptoms, highlighting RabGGT-β's aggravating role.
- Mitochondrial dysfunction appeared early in all models, suggesting it as a key contributor to myopathy before clinical signs, linking mevalonate pathway disruption to disease.