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Review

Relationship of S100 Proteins with Neuroinflammation

by
Mario García-Domínguez
1,2,3
1
Program of Immunology and Immunotherapy, CIMA-Universidad de Navarra, 31008 Pamplona, Spain
2
Department of Immunology and Immunotherapy, Clínica Universidad de Navarra, 31008 Pamplona, Spain
3
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain
Biomolecules 2025, 15(8), 1125; https://doi.org/10.3390/biom15081125
Submission received: 7 July 2025 / Revised: 24 July 2025 / Accepted: 4 August 2025 / Published: 4 August 2025

Abstract

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’s disease, multiple sclerosis, and Parkinson’s 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.
Keywords: S100 proteins; pro-inflammatory cytokines; CNS; glial cells; EF-hand motif; RAGE S100 proteins; pro-inflammatory cytokines; CNS; glial cells; EF-hand motif; RAGE

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MDPI and ACS Style

García-Domínguez, M. Relationship of S100 Proteins with Neuroinflammation. Biomolecules 2025, 15, 1125. https://doi.org/10.3390/biom15081125

AMA Style

García-Domínguez M. Relationship of S100 Proteins with Neuroinflammation. Biomolecules. 2025; 15(8):1125. https://doi.org/10.3390/biom15081125

Chicago/Turabian Style

García-Domínguez, Mario. 2025. "Relationship of S100 Proteins with Neuroinflammation" Biomolecules 15, no. 8: 1125. https://doi.org/10.3390/biom15081125

APA Style

García-Domínguez, M. (2025). Relationship of S100 Proteins with Neuroinflammation. Biomolecules, 15(8), 1125. https://doi.org/10.3390/biom15081125

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