{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:39:02Z","timestamp":1791909542416,"version":"4.3.4"},"reference-count":174,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T00:00:00Z","timestamp":1755993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Education PRIN-2022","award":["2022PFFPBL"],"award-info":[{"award-number":["2022PFFPBL"]}]},{"name":"Italian Ministry of Education PRIN-2022","award":["20225YC53P"],"award-info":[{"award-number":["20225YC53P"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>CD44, a structurally diverse cell-surface glycoprotein, plays a multifaceted and indispensable role in neural tissue across both physiological and pathological conditions. It orchestrates complex cell\u2013extracellular matrix interactions and intracellular signaling through its variant isoforms and post-translational modifications and is broadly expressed in neural stem\/progenitor cells, microglia, astrocytes, and selected neuronal populations. The interactions of CD44 with ligands such as hyaluronan and osteopontin regulate critical cellular functions, including migration, differentiation, inflammation, and synaptic plasticity. In microglia and macrophages, CD44 mediates immune signaling and phagocytic activity, and it is dynamically upregulated in neuroinflammatory diseases, particularly through pathways involving Toll-like receptor 4. CD44 expression in astrocytes is abundant during central nervous system development and in diseases, contributing to glial differentiation, reactive astrogliosis, and scar formation. Though its expression is less prominent in mature neurons, CD44 supports neural plasticity, circuit organization, and injury-induced repair mechanisms. Additionally, its expression at nervous system barriers, such as the blood\u2013brain barrier, underscores its role in regulating vascular permeability during inflammation and ischemia. Collectively, CD44 emerges as a critical integrator of neural cell function and intercellular communication. Although the roles of CD44 in glial cells appear to be similar to those explored in other tissues, the expression of this molecule and its variants on neurons reveals peculiar functions. Elucidating the cell-type-specific roles and regulation of CD44 variants may offer novel therapeutic strategies for diverse neurological disorders.<\/jats:p>","DOI":"10.3390\/ijms26178223","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:10:36Z","timestamp":1756080636000},"page":"8223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Expression of CD44 and Its Spliced Variants: Innate and Inducible Roles in Nervous Tissue Cells and Their Environment"],"prefix":"10.3390","volume":"26","author":[{"given":"Maria Concetta","family":"Geloso","sequence":"first","affiliation":[{"name":"Section of Human Anatomy, Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"},{"name":"Gemelli Science and Technology Park (GSTeP)-Organoids Research Core Facility, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7455-4290","authenticated-orcid":false,"given":"Francesco","family":"Ria","sequence":"additional","affiliation":[{"name":"Section of General Pathology, Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Corvino","sequence":"additional","affiliation":[{"name":"Section of Human Anatomy, Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6608-3388","authenticated-orcid":false,"given":"Gabriele","family":"Di Sante","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Section of Human, Clinical and Forensic Anatomy, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1136\/mp.52.4.189","article-title":"CD44 Cell Adhesion Molecules","volume":"52","author":"Goodison","year":"1999","journal-title":"Mol. 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