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

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Prospects for mTOR-mediated functional repair after central nervous system trauma. / Berry, Martin; Ahmed, Zubair; Morgan-Warren, Peter; Fulton, Daniel; Logan, Ann.

In: Neurobiology of Disease, Vol. 85, 01.2016, p. 99-110.

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@article{7df015ec2db14aa1833be60ad888d3dd,
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.",
keywords = "mTOR, Spinal cord injury, Axogenesis, Axon Regeneration, myelination",
author = "Martin Berry and Zubair Ahmed and Peter Morgan-Warren and Daniel Fulton and Ann Logan",
year = "2016",
month = jan,
doi = "10.1016/j.nbd.2015.10.002",
language = "English",
volume = "85",
pages = "99--110",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Prospects for mTOR-mediated functional repair after central nervous system trauma

AU - Berry, Martin

AU - Ahmed, Zubair

AU - Morgan-Warren, Peter

AU - Fulton, Daniel

AU - Logan, Ann

PY - 2016/1

Y1 - 2016/1

N2 - 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.

AB - 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.

KW - mTOR

KW - Spinal cord injury

KW - Axogenesis

KW - Axon Regeneration

KW - myelination

U2 - 10.1016/j.nbd.2015.10.002

DO - 10.1016/j.nbd.2015.10.002

M3 - Review article

VL - 85

SP - 99

EP - 110

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

ER -