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S100 calcium binding protein B (S100B) is a member of the S100 family of EF-hand calcium-binding proteins, primarily synthesized and secreted by astrocytes in the central nervous system (UniProt P04271). At physiological concentrations, S100B acts as a neurotrophic factor promoting neurite outgrowth and neuronal survival; however, at high concentrations, it functions as a pro-inflammatory cytokine and a damage-associated molecular pattern (DAMP) molecule (PMID: 15569905). Elevated levels of S100B are associated with neuroinflammation and neurodegeneration, often exerting pathological effects through the Receptor for Advanced Glycation End-products (RAGE) (PMID: 18436346). In clinical practice, S100B is widely used as a biomarker for brain injury, stroke, and certain cancers like melanoma (PMID: 23434470). Therapeutic strategies targeting S100B include the use of small molecules like arundic acid (ONO-2506) to specifically inhibit its synthesis in glial cells (PMID: 12467365). Other compounds, such as pentamidine, act by directly binding to the protein and blocking its interaction with downstream targets. Modulating S100B levels or activity is being explored to mitigate neuroinflammatory damage in conditions such as Alzheimer's disease and amyotrophic lateral sclerosis.
Inhibition of S100B synthesis in astrocytes, direct binding and inhibition of S100B protein activity, and blockade of S100B-RAGE interaction.
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