title: Releasing 'brakes' to nerve regeneration: intrinsic molecular targets.
abstract: Restoring critical neuronal architecture after peripheral nerve injury is challenging. Although immediate regenerative responses to peripheral axon injury involve the synthesis of regeneration-associated proteins in neurons and Schwann cells, an unfavorable balance between growth facilitatory and growth inhibitory signaling impairs the growth continuum of injured peripheral nerves. Molecules involved with the signaling network of tumor suppressors play crucial roles in shifting the balance between growth and restraint during axon regeneration. An understanding of the molecular framework of tumor suppressor molecules in injured neurons and its impact on stage-specific regeneration events may expose therapeutic intervention points. In this review we discuss how signaling networks of the specific tumor suppressors PTEN, Rb1, p53, p27 and p21 are altered in injured peripheral nerves and how this impacts peripheral nerve regeneration. Insights into the roles and importance of these pathways may open new avenues for improving the neurological deficits associated with nerve injury.
authors.affiliation: Division of Neurology & Neuroscience and Mental Health Institute, Department of Medicine, University of Alberta, 7-123A Clinical Sciences Building, Edmonton, AB, T6G 2G3, Canada.
authors.forename: Anand
authors.initials: A
authors.lastname: Krishnan
authors.affiliation: Division of Neurology & Neuroscience and Mental Health Institute, Department of Medicine, University of Alberta, 7-123A Clinical Sciences Building, Edmonton, AB, T6G 2G3, Canada.
authors.forename: Arul
authors.initials: A
authors.lastname: Duraikannu
authors.affiliation: Division of Neurology & Neuroscience and Mental Health Institute, Department of Medicine, University of Alberta, 7-123A Clinical Sciences Building, Edmonton, AB, T6G 2G3, Canada.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Zochodne
mesh_terms: D000818:Animals; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009416:Nerve Regeneration; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27; D054462:p21-Activated Kinases; D051059:PTEN Phosphohydrolase
keywords: PTEN; Rb1; p21; p27; p53; peripheral nerve