ROCK signaling at the crossroads of redox stress, mitochondrial dynamics, and metabolic disease - PubMed
5 days ago
- #Metabolic disease
- #ROCK signaling
- #Mitochondrial dynamics
- ROCK1 and ROCK2 are central to cytoskeletal dynamics, redox regulation, and mitochondrial quality control.
- Dysregulated ROCK signaling leads to mitochondrial fragmentation, oxidative stress, and metabolic inflexibility, contributing to diseases like diabetes and obesity.
- ROCK1 regulates mitochondrial dynamics by phosphorylating Drp1 and suppressing the AMPK-PGC-1α pathway, impairing fatty acid oxidation and mitochondrial biogenesis.
- Inhibition of ROCK can restore mitochondrial structure, energy metabolism, and redox balance in organs like the heart, kidney, and liver.
- ROCK2 has complementary roles in immune regulation and fibrotic remodeling, with selective inhibitors showing clinical success.
- Metabolic drugs like statins and GLP-1 receptor agonists can indirectly reduce ROCK activity, offering potential therapeutic strategies.
- Future research should focus on ROCK1-specific signaling, tissue-targeted inhibitors, and combining ROCK modulation with metabolic or antioxidant therapies.