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Thread: Rho Signaling Pathway Targeted to Promote Spinal Cord Repair

  1. #1

    Rho Signaling Pathway Targeted to Promote Spinal Cord Repair

    *this is only an abstract from last week's Journal of Neuroscience. Dr. Lisa McKerracher's got things moving up here in her labs at the Univerity de Montreal. maybe Dr. Y can hook up the full article, even move it to the SCI Research section if its more appropriate. and a big shout out to Coolbab64 for pointing this out.


    Rho Signaling Pathway Targeted to Promote Spinal Cord Repair

    (Pauline Dergham1, Benjamin Ellezam1, Charles Essagian1, Hovsep Avedissian2, William D. Lubell2, and Lisa McKerracher1
    Départements de 1 Pathologie et Biologie Cellulaire and 2 Chimie, Université de Montréal, Montréal, Québec, H3T 1J4, Canada)

    The Rho signaling pathway regulates the cytoskeleton and motility and plays an important role in neuronal growth inhibition. Here we demonstrate that inactivation of Rho or its downstream target Rho-associated kinase (ROK) stimulated neurite growth in primary cells of cortical neurons plated on myelin or chondroitin sulfate proteoglycan substrates. Furthermore, treatment either with C3 transferase (C3) to inactivate Rho or with Y27632 to inhibit ROK was sufficient to stimulate axon regeneration and recovery of hindlimb function after spinal cord injury (SCI) in adult mice. Injured mice were treated with a single injection of Rho or Rho-associated kinase inhibitors delivered in a protein adhesive at the lesion site. Treated animals showed long-distance regeneration of anterogradely labeled corticospinal axons and increased levels of GAP-43 mRNA in the motor cortex. Behaviorally, inactivation of Rho pathway induced rapid recovery of locomotion and progressive recuperation of forelimb-hindlimb coordination. These findings provide evidence that the Rho signaling pathway is a potential target for therapeutic interventions after spinal cord injury.

    Key words: Rho GTPase; Rho-associated kinase; C3; Y27632; corticospinal tract; regeneration; BBB behavior scale; GAP-43; mouse

    "work like you don't need the money - love like you've never been hurt - dance like nobody's watching"

  2. #2
    Again and again I am impressed with Dr. McKerracher's efforts.

    I think she will be a big player in the future our recovery.

    Onward and Upward!

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