Tissue plasminogen activator promotes axonal outgrowth on CNS myelin after conditioned injury.
Following CNS injury, myelin-associated inhibitors represent major obstacles to axonal regeneration and functional recovery. The following study suggests that the proteolytic enzyme tissue plasminogen activator (tPA) plays a major function in 'conditioning-injury induced' axon regeneration. In this paradigm, prior peripheral nerve injury leads to an enhanced ability of sensory neurons to regenerate their central axons in the presence of the CNS inhibitory microenvironment. tPA is widely expressed by CNS and PNS neurons and plays major roles in synaptic reorganization and plasticity. This study shows that cultured neurons from mice deficient in tPA, in contrast to wild-type mice, fail to undergo conditioning-injury induced axonal regeneration in the presence of purified myelin membranes. Interestingly, neurons from mice deficient in plasminogen, the best known substrate for tPA, showed active axon regeneration. These results suggest a novel plasminogen-independent role for tPA in promoting axonal regeneration on CNS myelin.
Minor
Kenneth
K
Department of Biochemistry & Molecular Genetics, University of Colorado Denver, School of Medicine, Aurora, Colorado 8004, USA.
Phillips
Jacob
J
Seeds
Nicholas W
NW
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000473:pathology*; D005727:Ganglia, Spinal / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000737:chemistry / Q000502:physiology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010958:Plasminogen / Q000172:deficiency; D020426:Sciatic Neuropathy / Q000473:pathology*; D010959:Tissue Plasminogen Activator / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism
D014404:Tubulin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator