{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nS100B is an EF‐hand calcium‐binding protein predominantly expressed by astrocytes that exerts multifaceted intracellular and extracellular functions. At the cellular level, it modulates energy metabolism, cytoskeletal organization, proliferation, migration, and differentiation. In a concentration‐dependent manner, nanomolar levels of extracellular S100B exert trophic effects—stimulating neurite outgrowth and promoting neuronal survival during development—whereas micromolar concentrations trigger proinflammatory cytokine expression and apoptosis. In addition, S100B interacts with multiple binding partners such as the receptor for advanced glycation end products (RAGE) and even key regulators like the tumor suppressor p53, with these interactions influencing cellular signaling pathways (e.g., phosphatidylinositol 3‐kinase/Akt, NF‑κB, JNK, and GSK3β) and modulating glial as well as neuronal responses. This intricate interplay has been demonstrated by studies that mapped S100B’s binding epitopes and showed how S100B disrupts p53 tetramerization, thereby affecting p53‐mediated cell‐cycle control and apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, S100B has been extensively evaluated as a biomarker for a broad spectrum of neurological and neurodegenerative conditions. Elevated levels in cerebrospinal fluid and serum are associated with traumatic brain injury, ischemic stroke, Alzheimer’s and Parkinson’s diseases, and have even been implicated in psychiatric disorders such as schizophrenia and mood disorders. In addition to brain injury where S100B levels may reflect astrocyte activation or damage, its measurement is proposed to aid in prognostication following head trauma and to monitor disease progression or treatment response in conditions ranging from metastatic melanoma to neuroinflammatory and neurodegenerative disorders. Importantly, studies have also highlighted extracerebral contributions—such as those arising from adipose tissue—to circulating S100B levels, emphasizing the need for careful interpretation when used in clinical settings."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "40"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond the central nervous system, S100B participates in modulating inflammatory responses and in the pathogenesis of peripheral disorders. In enteric glial cells, it has been implicated in host–bacteria cross‐talk and in mediating nitric oxide production in intestinal inflammatory conditions, while in neoplastic settings its interaction with p53 and other regulatory proteins can influence tumor cell survival and response to stress. Moreover, S100B is increasingly recognized as a component of complex intracellular feedback mechanisms that regulate its own expression and that of key effectors involved in both tissue repair and neurodegeneration, such as the hyperphosphorylation of tau proteins in Alzheimer’s disease. These mechanistic insights further substantiate the dual role of S100B as both a mediator and a marker of cellular distress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "41", "end_ref": "45"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Diego Gazzolo, Emanuela Marinoni, Romolo di Iorio, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Serum S100B is suitable for prediction and monitoring of response to chemoimmunotherapy in metastatic malignant melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Melanoma Res (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/00008390-200302000-00008"}], "href": "https://doi.org/10.1097/00008390-200302000-00008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12569284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12569284"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Linda E Pelinka, Eva Toegel, Walter Mauritz, et al. 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