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Here we investigate the role of protease activated receptor 2 (PAR2), a unique protease activated G protein\u2010coupled receptor, in myelin development and repair using the spinal cord as a model. Results demonstrate that genetic deletion of PAR2 accelerates myelin production, including higher proteolipid protein (PLP) levels in the spinal cord at birth and higher levels of myelin basic protein and thickened myelin sheaths in adulthood. Enhancements in spinal cord myelin with PAR2 loss\u2010of\u2010function were accompanied by increased numbers of Olig2\u2010 and CC1\u2010positive oligodendrocytes, as well as in levels of cyclic adenosine monophosphate (cAMP), and extracellular signal related kinase 1\/2 (ERK1\/2) signaling. Parallel promyelinating effects were observed after blocking PAR2 expression in purified oligodendrocyte cultures, whereas inhibiting adenylate cyclase reversed these effects. Conversely, PAR2 activation reduced PLP expression and this effect was prevented by brain derived neurotrophic factor (BDNF), a promyelinating growth factor that signals through cAMP. PAR2 knockout mice also showed improved myelin resiliency after traumatic spinal cord injury and an accelerated pattern of myelin regeneration after focal demyelination. These findings suggest that PAR2 is an important controller of myelin production and regeneration, both in the developing and adult spinal cord.<\/jats:p>","DOI":"10.1002\/glia.23215","type":"journal-article","created":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T15:05:45Z","timestamp":1505747145000},"page":"2070-2086","source":"Crossref","is-referenced-by-count":19,"title":["Protease activated receptor 2 controls myelin development, resiliency and repair"],"prefix":"10.1002","volume":"65","author":[{"given":"Hyesook","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation Rehabilitation Medicine Research Center Rochester Minnesota 55905"},{"name":"Department of Physiology and Biomedical Engineering Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Radulovic","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation Rehabilitation Medicine Research Center Rochester Minnesota 55905"},{"name":"Neurobiology of Disease Program, Mayo Clinic Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"Walters","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation Rehabilitation Medicine Research Center Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex R.","family":"Paulsen","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation Rehabilitation Medicine Research Center Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Drucker","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation Rehabilitation Medicine Research Center Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Starski","sequence":"additional","affiliation":[{"name":"Neurobiology of Disease Program, Mayo Clinic Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation Rehabilitation Medicine Research Center Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Fairlie","sequence":"additional","affiliation":[{"name":"ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, University of Queensland Brisbane Queensland 4072 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2395-589X","authenticated-orcid":false,"given":"Isobel 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