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PTEN Deletion Enhances the Regenerative Ability of Adult Corticospinal Neurons

Despite the essential role of the corticospinal tract (CST) in controlling voluntary movements, successful regeneration of large numbers of injured CST axons beyond a spinal cord lesion has never been achieved. Here we demonstrate a critical involvement of PTEN/mTOR in controlling the regenerative c...

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Autores principales: Liu, Kai, Lu, Yi, Lee, Jae K., Samara, Ramsey, Willenberg, Rafer, Sears-Kraxberger, Ilse, Tedeschi, Andrea, Park, Kevin Kyungsuk, Jin, Duo, Cai, Bin, Xu, Bengang, Connolly, Lauren, Steward, Oswald, Zheng, Binhai, He, Zhigang
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928871/
https://www.ncbi.nlm.nih.gov/pubmed/20694004
http://dx.doi.org/10.1038/nn.2603
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author Liu, Kai
Lu, Yi
Lee, Jae K.
Samara, Ramsey
Willenberg, Rafer
Sears-Kraxberger, Ilse
Tedeschi, Andrea
Park, Kevin Kyungsuk
Jin, Duo
Cai, Bin
Xu, Bengang
Connolly, Lauren
Steward, Oswald
Zheng, Binhai
He, Zhigang
author_facet Liu, Kai
Lu, Yi
Lee, Jae K.
Samara, Ramsey
Willenberg, Rafer
Sears-Kraxberger, Ilse
Tedeschi, Andrea
Park, Kevin Kyungsuk
Jin, Duo
Cai, Bin
Xu, Bengang
Connolly, Lauren
Steward, Oswald
Zheng, Binhai
He, Zhigang
author_sort Liu, Kai
collection PubMed
description Despite the essential role of the corticospinal tract (CST) in controlling voluntary movements, successful regeneration of large numbers of injured CST axons beyond a spinal cord lesion has never been achieved. Here we demonstrate a critical involvement of PTEN/mTOR in controlling the regenerative capacity of mouse corticospinal neurons. Upon the completion of development, the regrowth potential of CST axons lost and this is accompanied by a down-regulation of mTOR activity in corticospinal neurons. Axonal injury further diminishes neuronal mTOR activity in these neurons. Forced up-regulation of mTOR activity in corticospinal neurons by conditional deletion of PTEN, a negative regulator of mTOR, enhances compensatory sprouting of uninjured CST axons and even more strikingly, enables successful regeneration of a cohort of injured CST axons past a spinal cord lesion. Furthermore, these regenerating CST axons possess the ability to reform synapses in spinal segments distal to the injury. Thus, modulating neuronal intrinsic PTEN/mTOR activity represents a potential therapeutic strategy for promoting axon regeneration and functional repair after adult spinal cord injury.
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spelling pubmed-29288712011-03-01 PTEN Deletion Enhances the Regenerative Ability of Adult Corticospinal Neurons Liu, Kai Lu, Yi Lee, Jae K. Samara, Ramsey Willenberg, Rafer Sears-Kraxberger, Ilse Tedeschi, Andrea Park, Kevin Kyungsuk Jin, Duo Cai, Bin Xu, Bengang Connolly, Lauren Steward, Oswald Zheng, Binhai He, Zhigang Nat Neurosci Article Despite the essential role of the corticospinal tract (CST) in controlling voluntary movements, successful regeneration of large numbers of injured CST axons beyond a spinal cord lesion has never been achieved. Here we demonstrate a critical involvement of PTEN/mTOR in controlling the regenerative capacity of mouse corticospinal neurons. Upon the completion of development, the regrowth potential of CST axons lost and this is accompanied by a down-regulation of mTOR activity in corticospinal neurons. Axonal injury further diminishes neuronal mTOR activity in these neurons. Forced up-regulation of mTOR activity in corticospinal neurons by conditional deletion of PTEN, a negative regulator of mTOR, enhances compensatory sprouting of uninjured CST axons and even more strikingly, enables successful regeneration of a cohort of injured CST axons past a spinal cord lesion. Furthermore, these regenerating CST axons possess the ability to reform synapses in spinal segments distal to the injury. Thus, modulating neuronal intrinsic PTEN/mTOR activity represents a potential therapeutic strategy for promoting axon regeneration and functional repair after adult spinal cord injury. 2010-08-08 2010-09 /pmc/articles/PMC2928871/ /pubmed/20694004 http://dx.doi.org/10.1038/nn.2603 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Liu, Kai
Lu, Yi
Lee, Jae K.
Samara, Ramsey
Willenberg, Rafer
Sears-Kraxberger, Ilse
Tedeschi, Andrea
Park, Kevin Kyungsuk
Jin, Duo
Cai, Bin
Xu, Bengang
Connolly, Lauren
Steward, Oswald
Zheng, Binhai
He, Zhigang
PTEN Deletion Enhances the Regenerative Ability of Adult Corticospinal Neurons
title PTEN Deletion Enhances the Regenerative Ability of Adult Corticospinal Neurons
title_full PTEN Deletion Enhances the Regenerative Ability of Adult Corticospinal Neurons
title_fullStr PTEN Deletion Enhances the Regenerative Ability of Adult Corticospinal Neurons
title_full_unstemmed PTEN Deletion Enhances the Regenerative Ability of Adult Corticospinal Neurons
title_short PTEN Deletion Enhances the Regenerative Ability of Adult Corticospinal Neurons
title_sort pten deletion enhances the regenerative ability of adult corticospinal neurons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928871/
https://www.ncbi.nlm.nih.gov/pubmed/20694004
http://dx.doi.org/10.1038/nn.2603
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