Neuroscience Forefront ReviewPeripheral axon regrowth: New molecular approaches

- Peripheral nerve regeneration is not as successful as generally portrayed.
- Regeneration involves coordinated responses of the perikaryon and outgrowing axon.
- Significant intrinsic barriers to regrowth dampen the regenerative response.
- PI3K-Akt, inhibited by the phosphatase PTEN, is a critical regenerative pathway.
- Knockdown or inhibition of PTEN enhances initial axon outgrowth.

Peripheral nerves, essential connections between the brain, spinal cord and body, do not regenerate as well as generally reported. Identifying new strategies to facilitate regeneration is essential to reversing neurological deficits from nerve injuries or disease. This review will discuss several selected and novel molecular insights into peripheral nerve trunk repair and axon regrowth that have the potential to improve regenerative success. Of particular interest is the phosphatidylinositol 3-kinase (PI3K)-Akt pathway in peripheral neurons, inhibited by the constitutively expressed phosphatase tumor suppressor PTEN. Knockdown or inhibition of PTEN is associated with robust sprouting of adult sensory neurons in vitro and in vivo, additive to the accelerated outgrowth offered by the preconditioning effect. This sprouting response, if spatially and temporally constrained, may provide potent regrowth initiation, of interest in otherwise untreatable nerve damage.