Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月26日

查看全文
  • 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 Hees,
  • Zhuqiu Xu,
  • Xirui Chen,
  • Lee B. Barrett,
  • Laura Perrault,
  • Roshan Pandey,
  • Kathleen Zhang,
  • Aparna Bhaduri,
  • Zhigang He,
  • Harley I. Kornblum,
  • Jed Hubbs,
  • Clifford J. Woolf

摘要

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.