{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:46:16Z","timestamp":1790682376240,"version":"4.1.0"},"reference-count":173,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Education, University and Research","award":["2015KRYSJN"],"award-info":[{"award-number":["2015KRYSJN"]}]},{"name":"Italian Ministry of Education, University and Research","award":["2017XKJTLW_001"],"award-info":[{"award-number":["2017XKJTLW_001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tumor necrosis factor (TNF)-\u03b1-stimulated gene 6 (TSG-6), the first soluble chemokine-binding protein to be identified in mammals, inhibits chemotaxis and transendothelial migration of neutrophils and attenuates the inflammatory response of dendritic cells, macrophages, monocytes, and T cells. This immunoregulatory protein is a pivotal mediator of the therapeutic efficacy of mesenchymal stem\/stromal cells (MSC) in diverse pathological conditions, including neuroinflammation. However, TSG-6 is also constitutively expressed in some tissues, such as the brain and spinal cord, and is generally upregulated in response to inflammation in monocytes\/macrophages, dendritic cells, astrocytes, vascular smooth muscle cells and fibroblasts. Due to its ability to modulate sterile inflammation, TSG-6 exerts protective effects in diverse degenerative and inflammatory diseases, including brain disorders. Emerging evidence provides insights into the potential use of TSG-6 as a peripheral diagnostic and\/or prognostic biomarker, especially in the context of ischemic stroke, whereby the pathobiological relevance of this protein has also been demonstrated in patients. Thus, in this review, we will discuss the most recent data on the involvement of TSG-6 in neurodegenerative diseases, particularly focusing on relevant anti-inflammatory and immunomodulatory functions. Furthermore, we will examine evidence suggesting novel therapeutic opportunities that can be afforded by modulating TSG-6-related pathways in neuropathological contexts and, most notably, in stroke.<\/jats:p>","DOI":"10.3390\/ijms24021162","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T02:09:39Z","timestamp":1673230179000},"page":"1162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Tumor Necrosis Factor (TNF)-\u03b1-Stimulated Gene 6 (TSG-6): A Promising Immunomodulatory Target in Acute Neurodegenerative Diseases"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1887-2854","authenticated-orcid":false,"given":"Daniele","family":"La Russa","sequence":"first","affiliation":[{"name":"Section of Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Di Santo","sequence":"additional","affiliation":[{"name":"Section of Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Lizasoain","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n Neurovascular, Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Medicina, Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Universidad Complutense de Madrid, and Instituto de Investigaci\u00f3n Hospital 12 de Octubre (Imas12), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Moraga","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n Neurovascular, Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Medicina, Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Universidad Complutense de Madrid, and Instituto de Investigaci\u00f3n Hospital 12 de Octubre (Imas12), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8540-6218","authenticated-orcid":false,"given":"Giacinto","family":"Bagetta","sequence":"additional","affiliation":[{"name":"Section of Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7513-3495","authenticated-orcid":false,"given":"Diana","family":"Amantea","sequence":"additional","affiliation":[{"name":"Section of Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, regional, and national burden of stroke and its risk factors, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"20","author":"Feigin","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1016\/S0140-6736(20)32163-2","article-title":"Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: Systematic review and meta-analysis of individual patient data","volume":"396","author":"Thomalla","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1056\/NEJMoa1813046","article-title":"Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke","volume":"380","author":"Ma","year":"2019","journal-title":"N. 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