Open Access

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

  • Authors:
    • Yutong Chen
    • Zurui Liu
    • Chen Liu
    • Daqian Yang
    • Mengmeng Xiao
    • Zhengqian Li
    • Zhengwei Xie
  • View Affiliations

  • Published online on: June 26, 2025     https://doi.org/10.3892/ijmm.2025.5569
  • Article Number: 128
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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September-2025
Volume 56 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Chen Y, Liu Z, Liu C, Yang D, Xiao M, Li Z and Xie Z: GW8510 alleviates muscle atrophy and skeletal muscle dysfunction in mice through AMPK/PGC1&alpha; signaling. Int J Mol Med 56: 128, 2025.
APA
Chen, Y., Liu, Z., Liu, C., Yang, D., Xiao, M., Li, Z., & Xie, Z. (2025). GW8510 alleviates muscle atrophy and skeletal muscle dysfunction in mice through AMPK/PGC1&alpha; signaling. International Journal of Molecular Medicine, 56, 128. https://doi.org/10.3892/ijmm.2025.5569
MLA
Chen, Y., Liu, Z., Liu, C., Yang, D., Xiao, M., Li, Z., Xie, Z."GW8510 alleviates muscle atrophy and skeletal muscle dysfunction in mice through AMPK/PGC1&alpha; signaling". International Journal of Molecular Medicine 56.3 (2025): 128.
Chicago
Chen, Y., Liu, Z., Liu, C., Yang, D., Xiao, M., Li, Z., Xie, Z."GW8510 alleviates muscle atrophy and skeletal muscle dysfunction in mice through AMPK/PGC1&alpha; signaling". International Journal of Molecular Medicine 56, no. 3 (2025): 128. https://doi.org/10.3892/ijmm.2025.5569