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Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury.

Contusive spinal cord injury leads to a variety of disabilities owing to limited neuronal regeneration and functional plasticity. It is well established that an upregulation of glial-derived chondroitin sulphate proteoglycans (CSPGs) within the glial scar and perineuronal net creates a barrier to ax... Full description

Journal Title: Nature February 19, 2015, Vol.518(7539), pp.404-408
Main Author: Lang, Bradley T
Other Authors: Cregg, Jared M , Depaul, Marc A , Tran, Amanda P , Xu, Kui , Dyck, Scott M , Madalena, Kathryn M , Brown, Benjamin P , Weng, Yi-Lan , Li, Shuxin , Karimi-Abdolrezaee, Soheila , Busch, Sarah A , Shen, Yingjie , Silver, Jerry
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1476-4687 ; DOI: 10.1038/nature13974
Link: http://search.proquest.com/docview/1657318649/?pq-origsite=primo
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title: Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury.
format: Article
creator:
  • Lang, Bradley T
  • Cregg, Jared M
  • Depaul, Marc A
  • Tran, Amanda P
  • Xu, Kui
  • Dyck, Scott M
  • Madalena, Kathryn M
  • Brown, Benjamin P
  • Weng, Yi-Lan
  • Li, Shuxin
  • Karimi-Abdolrezaee, Soheila
  • Busch, Sarah A
  • Shen, Yingjie
  • Silver, Jerry
subjects:
  • Amino Acid Sequence–Metabolism
  • Animals–Chemistry
  • Chondroitin Sulfate Proteoglycans–Drug Effects
  • Extracellular Matrix–Metabolism
  • Female–Drug Effects
  • Growth Cones–Physiology
  • Humans–Drug Effects
  • Mice–Drug Effects
  • Molecular Sequence Data–Antagonists & Inhibitors
  • Nerve Regeneration–Chemistry
  • Protein Binding–Metabolism
  • Rats–Metabolism
  • Rats, Sprague-Dawley–Pathology
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2–Pathology
  • Spinal Cord Injuries–Pathology
  • Chondroitin Sulfate Proteoglycans
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
ispartof: Nature, February 19, 2015, Vol.518(7539), pp.404-408
description: Contusive spinal cord injury leads to a variety of disabilities owing to limited neuronal regeneration and functional plasticity. It is well established that an upregulation of glial-derived chondroitin sulphate proteoglycans (CSPGs) within the glial scar and perineuronal net creates a barrier to axonal regrowth and sprouting (1-5). Protein tyrosine phosphatase [sigma] (PTP[sigma]), along with its sister phosphatase leukocyte common antigen-related (LAR) and the nogo receptors 1 and 3 (NgR), have recently been identified as receptors for the inhibitory glycosylated side chains of CSPGs (6-8). Here we find in rats that PTP[sigma] has a critical role in converting growth cones into a dystrophic state by tightly stabilizing them within CSPG-rich substrates. We generated a membrane-permeable peptide mimetic of the PTP[sigma] wedge domain that binds to PTP[sigma] and relieves CSPG-mediated inhibition. Systemic delivery of this peptide over weeks restored substantial serotonergic innervation to the spinal cord below the level of injury and facilitated functional recovery of both locomotor and urinary systems. Our results add a new layer of understanding to the critical role of PTP[sigma] in mediating the growth-inhibited state of neurons due to CSPGs within the injured adult spinal cord.
language: eng
source:
identifier: E-ISSN: 1476-4687 ; DOI: 10.1038/nature13974
fulltext: fulltext
issn:
  • 14764687
  • 1476-4687
url: Link


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titleModulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury.
creatorLang, Bradley T ; Cregg, Jared M ; Depaul, Marc A ; Tran, Amanda P ; Xu, Kui ; Dyck, Scott M ; Madalena, Kathryn M ; Brown, Benjamin P ; Weng, Yi-Lan ; Li, Shuxin ; Karimi-Abdolrezaee, Soheila ; Busch, Sarah A ; Shen, Yingjie ; Silver, Jerry
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ispartofNature, February 19, 2015, Vol.518(7539), pp.404-408
identifierE-ISSN: 1476-4687 ; DOI: 10.1038/nature13974
subjectAmino Acid Sequence–Metabolism ; Animals–Chemistry ; Chondroitin Sulfate Proteoglycans–Drug Effects ; Extracellular Matrix–Metabolism ; Female–Drug Effects ; Growth Cones–Physiology ; Humans–Drug Effects ; Mice–Drug Effects ; Molecular Sequence Data–Antagonists & Inhibitors ; Nerve Regeneration–Chemistry ; Protein Binding–Metabolism ; Rats–Metabolism ; Rats, Sprague-Dawley–Pathology ; Receptor-Like Protein Tyrosine Phosphatases, Class 2–Pathology ; Spinal Cord Injuries–Pathology ; Chondroitin Sulfate Proteoglycans ; Receptor-Like Protein Tyrosine Phosphatases, Class 2
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descriptionContusive spinal cord injury leads to a variety of disabilities owing to limited neuronal regeneration and functional plasticity. It is well established that an upregulation of glial-derived chondroitin sulphate proteoglycans (CSPGs) within the glial scar and perineuronal net creates a barrier to axonal regrowth and sprouting (1-5). Protein tyrosine phosphatase [sigma] (PTP[sigma]), along with its sister phosphatase leukocyte common antigen-related (LAR) and the nogo receptors 1 and 3 (NgR), have recently been identified as receptors for the inhibitory glycosylated side chains of CSPGs (6-8). Here we find in rats that PTP[sigma] has a critical role in converting growth cones into a dystrophic state by tightly stabilizing them within CSPG-rich substrates. We generated a membrane-permeable peptide mimetic of the PTP[sigma] wedge domain that binds to PTP[sigma] and relieves CSPG-mediated inhibition. Systemic delivery of this peptide over weeks restored substantial serotonergic innervation to the spinal cord below the level of injury and facilitated functional recovery of both locomotor and urinary systems. Our results add a new layer of understanding to the critical role of PTP[sigma] in mediating the growth-inhibited state of neurons due to CSPGs within the injured adult spinal cord.
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authorLang, Bradley T ; Cregg, Jared M ; Depaul, Marc A ; Tran, Amanda P ; Xu, Kui ; Dyck, Scott M ; Madalena, Kathryn M ; Brown, Benjamin P ; Weng, Yi-Lan ; Li, Shuxin ; Karimi-Abdolrezaee, Soheila ; Busch, Sarah A ; Shen, Yingjie ; Silver, Jerry
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