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Sustained axon regeneration induced by co-deletion of PTEN and SOCS3

A formidable challenge in neural repair in the adult central nervous system (CNS) is the long distances that regenerating axons often need to travel in order to reconnect with their targets. Thus, a sustained capacity for axon regeneration is critical for achieving functional restoration. Although d...

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Autores principales: Sun, Fang, Park, Kevin K., Belin, Stephane, Wang, Dongqing, Lu, Tao, Chen, Gang, Zhang, Kang, Yeung, Cecil, Feng, Guoping, Yankner, Bruce A., He, Zhigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3240702/
https://www.ncbi.nlm.nih.gov/pubmed/22056987
http://dx.doi.org/10.1038/nature10594
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author Sun, Fang
Park, Kevin K.
Belin, Stephane
Wang, Dongqing
Lu, Tao
Chen, Gang
Zhang, Kang
Yeung, Cecil
Feng, Guoping
Yankner, Bruce A.
He, Zhigang
author_facet Sun, Fang
Park, Kevin K.
Belin, Stephane
Wang, Dongqing
Lu, Tao
Chen, Gang
Zhang, Kang
Yeung, Cecil
Feng, Guoping
Yankner, Bruce A.
He, Zhigang
author_sort Sun, Fang
collection PubMed
description A formidable challenge in neural repair in the adult central nervous system (CNS) is the long distances that regenerating axons often need to travel in order to reconnect with their targets. Thus, a sustained capacity for axon regeneration is critical for achieving functional restoration. Although deletion of either Phosphatase and tensin homolog (PTEN), a negative regulator of mammalian target of rapamycin (mTOR), or suppressor of cytokine signaling 3 (SOCS3), a negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, in adult retinal ganglion cells (RGCs) individually promoted significant optic nerve regeneration, such regrowth tapered off around two weeks after the crush injury(1,2). Remarkably, we now find that simultaneous deletion of both PTEN and SOCS3 enables robust and sustained axon regeneration. We further show that PTEN and SOCS3 regulate two independent pathways that act synergistically to promote enhanced axon regeneration. Gene expression analyses suggest that double deletion not only results in the induction of many growth-related genes, but also allows RGCs to maintain the expression of a repertoire of genes at the physiological level after injury. Our results reveal concurrent activation of mTOR and STAT3 pathways as a key for sustaining long-distance axon regeneration in adult CNS, a crucial step toward functional recovery.
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spelling pubmed-32407022012-06-15 Sustained axon regeneration induced by co-deletion of PTEN and SOCS3 Sun, Fang Park, Kevin K. Belin, Stephane Wang, Dongqing Lu, Tao Chen, Gang Zhang, Kang Yeung, Cecil Feng, Guoping Yankner, Bruce A. He, Zhigang Nature Article A formidable challenge in neural repair in the adult central nervous system (CNS) is the long distances that regenerating axons often need to travel in order to reconnect with their targets. Thus, a sustained capacity for axon regeneration is critical for achieving functional restoration. Although deletion of either Phosphatase and tensin homolog (PTEN), a negative regulator of mammalian target of rapamycin (mTOR), or suppressor of cytokine signaling 3 (SOCS3), a negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, in adult retinal ganglion cells (RGCs) individually promoted significant optic nerve regeneration, such regrowth tapered off around two weeks after the crush injury(1,2). Remarkably, we now find that simultaneous deletion of both PTEN and SOCS3 enables robust and sustained axon regeneration. We further show that PTEN and SOCS3 regulate two independent pathways that act synergistically to promote enhanced axon regeneration. Gene expression analyses suggest that double deletion not only results in the induction of many growth-related genes, but also allows RGCs to maintain the expression of a repertoire of genes at the physiological level after injury. Our results reveal concurrent activation of mTOR and STAT3 pathways as a key for sustaining long-distance axon regeneration in adult CNS, a crucial step toward functional recovery. 2011-11-06 /pmc/articles/PMC3240702/ /pubmed/22056987 http://dx.doi.org/10.1038/nature10594 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
Sun, Fang
Park, Kevin K.
Belin, Stephane
Wang, Dongqing
Lu, Tao
Chen, Gang
Zhang, Kang
Yeung, Cecil
Feng, Guoping
Yankner, Bruce A.
He, Zhigang
Sustained axon regeneration induced by co-deletion of PTEN and SOCS3
title Sustained axon regeneration induced by co-deletion of PTEN and SOCS3
title_full Sustained axon regeneration induced by co-deletion of PTEN and SOCS3
title_fullStr Sustained axon regeneration induced by co-deletion of PTEN and SOCS3
title_full_unstemmed Sustained axon regeneration induced by co-deletion of PTEN and SOCS3
title_short Sustained axon regeneration induced by co-deletion of PTEN and SOCS3
title_sort sustained axon regeneration induced by co-deletion of pten and socs3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3240702/
https://www.ncbi.nlm.nih.gov/pubmed/22056987
http://dx.doi.org/10.1038/nature10594
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