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The mechanisms underlying the development of some forms of dementia, such as Alzheimer's disease (AD), are not yet completely elucidated with several competing hypotheses existing. During the closure of the critical period in the brain, significant compositional changes occur to the neural extracellular matrix (ECM). Specifically, condensed mesh\u2010like structures called perineuronal nets (PNNs) form around subsets of neurons and have a profound effect on axonal growth and limit neuronal plasticity. These PNNs act as a morphological checkpoint and can influence memory and cognition. Manipulating these important ECM structures may provide the key to reactivating plasticity and restoring memory, both of which are severely impaired in AD and other associated neurological diseases. This review explores the current understanding of how PNNs are manipulated and examines potential new methods for PNN modulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v176.18\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v176.18\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14672","type":"journal-article","created":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T10:05:00Z","timestamp":1553853900000},"page":"3611-3621","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["The potential of memory enhancement through modulation of perineuronal nets"],"prefix":"10.1111","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0044-4977","authenticated-orcid":false,"given":"James A.","family":"Duncan","sequence":"first","affiliation":[{"name":"School of Chemistry University of Leeds  Leeds 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