Improving peripheral nerve regeneration: from molecular mechanisms to potential therapeutic targets

Exp Neurol. 2014 Nov:261:826-35. doi: 10.1016/j.expneurol.2014.09.006. Epub 2014 Sep 16.

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.

Keywords: Animal studies; Molecular mechanisms; Nerve regeneration; Peripheral nerve injury; Therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cyclic AMP / genetics
  • Cyclic AMP / metabolism
  • Disease Models, Animal
  • Humans
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / genetics*
  • Peripheral Nervous System Diseases / therapy*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction / physiology*
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Immunologic Factors
  • Cyclic AMP
  • Phosphatidylinositol 3-Kinases
  • ras Proteins