Prospects for mTOR-mediated functional repair after central nervous system trauma

Research output: Contribution to journalReview articlepeer-review

Authors

Colleges, School and Institutes

Abstract

Recent research has suggested that the growth of central nervous system (CNS) axons during development is mediated through the PI3K/Akt/mammalian target of rapamycin (mTOR) intracellular signalling axis and that suppression of activity in this pathway occurs during maturity as levels of the phosphatase and tensin homologue (PTEN) rise and inhibit PI3K activation of mTOR, accounting for the failure of axon regeneration in the injured adult CNS. This hypothesis is supported by findings confirming that suppression of PTEN in experimental adult animals promotes impressive axon regeneration in the injured visual and corticospinal motor systems. This review focuses on these recent developments, discussing the therapeutic potential of a mTOR-based treatment aimed at promoting functional recovery in CNS trauma patients, recognising that to fulfil this ambition, the new therapy should aim to promote not only axon regeneration but also remyelination of regenerated axons, neuronal survival and re-innervation of denervated targets through accurate axonal guidance and synaptogenesis, all with minimal adverse effects. The translational challenges presented by the implementation of this new axogenic therapy are also discussed.

Details

Original languageEnglish
Pages (from-to)99-110
Number of pages11
JournalNeurobiology of Disease
Volume85
Early online date14 Oct 2015
Publication statusPublished - Jan 2016

Keywords

  • mTOR, Spinal cord injury, Axogenesis, Axon Regeneration, myelination

ASJC Scopus subject areas