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International journal of molecular medicine

International journal of molecular medicine

IF: 5.7
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GW8510 alleviates muscle atrophy and skeletal muscle dysfunction in mice through AMPK/PGC1α signaling

Published:1 September 2025 DOI: 10.3892/ijmm.2025.5569 PMID: 40576133
Yutong Chen,?Zurui Liu,?Chen Liu,?Daqian Yang,?Mengmeng Xiao,?Zhengqian Li,?Zhengwei Xie

Abstract

Preventing and restoring muscle loss and function is essential for elderly individuals. GW8510 may accelerate myotube differentiation. The present study aimed to investigate the protective effect of GW8510 (a CDK2 inhibitor) on muscle atrophy. Mouse models of muscle atrophy were induced by denervation, dexamethasone and glycerol. Muscle?to?body weight ratio, the cross?sectional area of muscles, grip strength, fatigue and serum levels of superoxide dismutase and creatine kinase were assessed. In vitro, a dexamethasone?induced C2C12 myotube atrophy model was used to evaluate mitochondrial function. Reverse transcription?quantitative PCR, immunoblotting and small interfering RNA transfection were performed to explore the potential molecular mechanisms following treatment with GW8510. GW8510 resulted in a significant increase in the gastrocnemius and soleus muscle ratios in denervation mice (7 and 3%, respectively), alongside an increase in cross?sectional area. Moreover, GW8510 significantly improved grip strength and superoxide dismutase activity, with similar protective effects in dexamethasone? and glycerol?induced muscle atrophy models. GW8510 decreased reactive oxygen species production, increased mitochondrial DNA copy number, maintained mitochondrial dynamics and enhanced antioxidant activity in C2C12 myotubes. Mechanistically, GW8510 significantly inhibited the expression of atrophy?associated markers F?box protein 32 and tripartite motif?containing 63 while activating AMPK (both P<0.01). The knockdown peroxisome proliferator?activated receptor?γ co?activator?1α (Pgc1α) negated the effects of GW8510. Overall, GW8510 mitigated muscle atrophy via the activation of the AMPK/PGC1α pathway. GW8510 could serve as a novel therapeutic agent for the prevention of muscle atrophy.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Dexamethasone 50-02-2 C22H29FO5 940 suppliers $20.00-$5210.50
Dexamethasone 50-02-2 C22H29FO5 940 suppliers $20.00-$5210.50
Dexamethasone 50-02-2 C22H29FO5 940 suppliers $20.00-$5210.50
Dexamethasone 50-02-2 C22H29FO5 940 suppliers $20.00-$5210.50

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