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Non-muscle myosin II inhibition at the site of axon injury increases axon regeneration

Author

Listed:
  • Keunjung Heo

    (Boston Children’s Hospital
    Harvard Medical School)

  • Tammy Szu-Yu Ho

    (Boston Children’s Hospital
    Harvard Medical School)

  • Xiangsunze Zeng

    (Boston Children’s Hospital
    Harvard Medical School)

  • Bruna Lenfers Turnes

    (Boston Children’s Hospital
    Harvard Medical School)

  • Maryam Arab

    (Boston Children’s Hospital
    Harvard Medical School)

  • Selwyn Jayakar

    (Boston Children’s Hospital
    Harvard Medical School)

  • Kuchuan Chen

    (Boston Children’s Hospital
    Harvard Medical School)

  • Georgios Kimourtzis

    (Boston Children’s Hospital
    Harvard Medical School)

  • Michael C. Condro

    (University of California)

  • Elisa Fazzari

    (University of California)

  • Xuan Song

    (Boston Children’s Hospital
    Harvard Medical School)

  • J. Tabitha Hees

    (Boston Children’s Hospital)

  • Zhuqiu Xu

    (Boston Children’s Hospital
    Harvard Medical School)

  • Xirui Chen

    (Boston Children’s Hospital
    Harvard Medical School)

  • Lee B. Barrett

    (Boston Children’s Hospital
    Harvard Medical School)

  • Laura Perrault

    (Boston Children’s Hospital)

  • Roshan Pandey

    (Boston Children’s Hospital
    Harvard Medical School)

  • Kathleen Zhang

    (Boston Children’s Hospital)

  • Aparna Bhaduri

    (University of California)

  • Zhigang He

    (Boston Children’s Hospital
    Harvard Medical School)

  • Harley I. Kornblum

    (University of California)

  • Jed Hubbs

    (Harvard Medical School)

  • Clifford J. Woolf

    (Boston Children’s Hospital
    Harvard Medical School)

Abstract

Motor axon regeneration following peripheral nerve injury is critical for motor recovery but therapeutic interventions enhancing this are not available. We conduct a phenotypic screen on human motor neurons and identified blebbistatin, a non-muscle myosin II inhibitor, as the most effective neurite outgrowth promotor. Despite its efficacy in vitro, its poor bioavailability limits in vivo application. We, therefore, utilize a blebbistatin analog, NMIIi2, to explore its therapeutic potential for promoting axon regeneration. Local NMIIi2 application directly to injured axons enhances regeneration in human motor neurons. Furthermore, following a sciatic nerve crush injury in male mice, local NMIIi2 administration to the axonal injury site facilitates motor neuron regeneration, muscle reinnervation, and functional recovery. NMIIi2 also promotes axon regeneration in sensory, cortical, and retinal ganglion neurons. These findings highlight the therapeutic potential of topical NMII inhibition for treating axon damage.

Suggested Citation

  • Keunjung Heo & Tammy Szu-Yu Ho & Xiangsunze Zeng & Bruna Lenfers Turnes & Maryam Arab & Selwyn Jayakar & Kuchuan Chen & Georgios Kimourtzis & Michael C. Condro & Elisa Fazzari & Xuan Song & J. Tabitha, 2025. "Non-muscle myosin II inhibition at the site of axon injury increases axon regeneration," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58303-6
    DOI: 10.1038/s41467-025-58303-6
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    References listed on IDEAS

    as
    1. Katherine M. Oliver & Danny M. Florez-Paz & Tudor Constantin Badea & George Z. Mentis & Vilas Menon & Joriene C. Nooij, 2021. "Molecular correlates of muscle spindle and Golgi tendon organ afferents," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    2. Haohao Wu & Charles Petitpré & Paula Fontanet & Anil Sharma & Carmelo Bellardita & Rolen M. Quadros & Paulo R. Jannig & Yiqiao Wang & J. Alexander Heimel & Kylie K. Y. Cheung & Simone Wanderoy & Yang , 2021. "Distinct subtypes of proprioceptive dorsal root ganglion neurons regulate adaptive proprioception in mice," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    Full references (including those not matched with items on IDEAS)

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