title: Improving peripheral nerve regeneration: from molecular mechanisms to potential therapeutic targets.
abstract: Peripheral nerve injury is common especially among young individuals. Although injured neurons have the ability to regenerate, the rate is slow and functional outcomes are often poor. Several potential therapeutic agents have shown considerable promise for improving the survival and regenerative capacity of injured neurons. These agents are reviewed within the context of their molecular mechanisms. The PI3K/Akt and Ras/ERK signaling cascades play a key role in neuronal survival. A number of agents that target these pathways, including erythropoietin, tacrolimus, acetyl-l-carnitine, n-acetylcysteine and geldanamycin have been shown to be effective. Trk receptor signaling events that up-regulate cAMP play an important role in enhancing the rate of axonal outgrowth. Agents that target this pathway including rolipram, testosterone, fasudil, ibuprofen and chondroitinase ABC hold considerable promise for human application. A tantalizing prospect is to combine different molecular targeting strategies in complementary pathways to optimize their therapeutic effects. Although further study is needed prior to human trials, these modalities could open a new horizon in the clinical arena that has so far been elusive.
authors.affiliation: Division of Physical Medicine and Rehabilitation, University of Alberta, Edmonton, Alberta, Canada; Centre for Neuroscience, University of Alberta, Canada. Electronic address: ming.chan@ualberta.ca.
authors.forename: K Ming
authors.initials: KM
authors.lastname: Chan
authors.affiliation: Division of Physical Medicine and Rehabilitation, University of Alberta, Edmonton, Alberta, Canada; Centre for Neuroscience, University of Alberta, Canada; Division of Plastic Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tessa
authors.initials: T
authors.lastname: Gordon
authors.affiliation: Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Zochodne
authors.affiliation: Division of Plastic Surgery, University of Alberta, Canada.
authors.forename: Hollie A
authors.initials: HA
authors.lastname: Power
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D009416:Nerve Regeneration / Q000187:drug effects / Q000235:genetics*; D010523:Peripheral Nervous System Diseases / Q000628:therapy*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D007155:Immunologic Factors; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; D018631:ras Proteins
keywords: Animal studies; Molecular mechanisms; Nerve regeneration; Peripheral nerve injury; Therapeutics