title: Prospects for mTOR-mediated functional repair after central nervous system trauma.
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.
authors.affiliation: Neurotrauma Research Group, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Berry
authors.affiliation: Neurotrauma Research Group, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address: z.ahmed.1@bham.ac.uk.
authors.forename: Zubair
authors.initials: Z
authors.lastname: Ahmed
authors.affiliation: Neurotrauma Research Group, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Morgan-Warren
authors.affiliation: Neurotrauma Research Group, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fulton
authors.affiliation: Neurotrauma Research Group, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Logan
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D006801:Humans; D009416:Nerve Regeneration / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D020196:Trauma, Nervous System / Q000503:physiopathology* / Q000628:therapy*
chemical_list: D058570:TOR Serine-Threonine Kinases
keywords: Axogenesis; Axon regeneration; Myelination; Spinal cord injury; mTOR