{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:03:22Z","timestamp":1791612202901,"version":"4.3.4"},"reference-count":214,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>S100 proteins, a family of Ca2+-binding proteins, play numerous roles in cellular processes such as proliferation, differentiation, and apoptosis. Recent evidence has highlighted their critical involvement in neuroinflammation, a pathological hallmark of various neurodegenerative disorders including Alzheimer\u2019s disease, multiple sclerosis, and Parkinson\u2019s disease. Among these proteins, S100B and S100A8\/A9 are particularly implicated in modulating inflammatory responses in the CNS. Acting as DAMPs, they interact with pattern recognition receptors like RAGE and TLRs, triggering pro-inflammatory signaling cascades and glial activation. While low concentrations of S100 proteins may support neuroprotective functions, increased levels are often associated with exacerbated inflammation and neuronal damage. This review explores the dualistic nature of S100 proteins in neuroinflammatory processes, their molecular interactions, and their potential as biomarkers and therapeutic targets in neurodegenerative disease management.<\/jats:p>","DOI":"10.3390\/biom15081125","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T15:30:06Z","timestamp":1754321406000},"page":"1125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Relationship of S100 Proteins with Neuroinflammation"],"prefix":"10.3390","volume":"15","author":[{"given":"Mario","family":"Garc\u00eda-Dom\u00ednguez","sequence":"first","affiliation":[{"name":"Program of Immunology and Immunotherapy, Center for Applied Medical Research University of Navarre, 31008 Pamplona, Spain"},{"name":"Department of Immunology and Immunotherapy, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"ref_1","first-page":"9999146","article-title":"Neuroinflammation: An Integrating Overview of Reactive-Neuroimmune Cell Interactions in Health and Disease","volume":"2021","author":"Udovin","year":"2021","journal-title":"Mediat. 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