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Severe motoneuron death and inefficient axon regeneration often result in devastating motor dysfunction. Newly formed axons need to extend through inhibitory scar tissue at the CNS-PNS transitional zone before entering into a pro-regenerative peripheral nerve trajectory. CSPGs are dominant suppressors in scar tissue and exert inhibition via neuronal receptors including PTP\u03c3. Previously, a small peptide memetic of the PTP\u03c3 wedge region named ISP (<jats:underline>I<\/jats:underline>ntracellular<jats:underline>S<\/jats:underline>igma<jats:underline>P<\/jats:underline>eptide) was generated and its capabilities to target PTP\u03c3 and relieve CSPG inhibition were validated. Here, we demonstrate that after ventral root avulsion and immediate re-implantation, modulation of PTP\u03c3 by systemic delivery of ISP remarkably enhanced regeneration. ISP treatment reduced motoneuron death, increased the number of axons regenerating across scar tissue, rebuilt healthy neuromuscular junctions and enhanced motor functional recovery. Our study shows that modulation of PTP\u03c3 is a potential therapeutic strategy for root avulsion.<\/jats:p>","DOI":"10.1038\/srep14923","type":"journal-article","created":{"date-parts":[[2015,10,14]],"date-time":"2015-10-14T10:29:31Z","timestamp":1444818571000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Enhanced regeneration and functional recovery after spinal root avulsion by manipulation of the proteoglycan receptor PTP\u03c3"],"prefix":"10.1038","volume":"5","author":[{"given":"Heng","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Ruven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liumin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T.","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry","family":"Silver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wutian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,10,14]]},"reference":[{"key":"BFsrep14923_CR1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3233\/RNN-2008-00438","volume":"26","author":"T Carlsedt","year":"2008","unstructured":"Carlsedt, T. 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