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HA synthesis is elevated following a wide variety of insults to the central nervous system (CNS) including neuroinflammatory disease, ischemia, and various forms of dementia. Recent studies have demonstrated that, in conjunction with increased HA synthesis, the expression and activities of hyaluronidases that digest HA are also elevated in the injured CNS. While high molecular weight forms of HA have their own functions that can be disrupted by hyaluronidases, digestion products of HA generated by these hyaluronidases have their own, distinct biological activities that can impact recovery from CNS damage. Here, we review some of the conditions and diseases in which hyaluronidase activity can play a role in preventing CNS repair and discuss the potential ways that hyaluronidase inhibitors could be used as therapeutic agents.<\/jats:p>","DOI":"10.1002\/pgr2.70036","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T04:40:36Z","timestamp":1758688836000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hyaluronidases as Targets for the Treatment of Neurological Diseases"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-6551","authenticated-orcid":false,"given":"Larry S.","family":"Sherman","sequence":"first","affiliation":[{"name":"Division of Neuroscience, Oregon National Primate Research Center Oregon Health &amp; Science University Beaverton Oregon USA"},{"name":"Department of Cell, Developmental &amp; Cancer Biology Oregon Health &amp; Science University Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Sorg","sequence":"additional","affiliation":[{"name":"Program in Neuroscience Washington State University Vancouver Washington USA"},{"name":"R.S. 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