IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58303-6.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58303-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-58303-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58303-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.