The S100B Protein: A Multifaceted Pathogenic Factor More Than a Biomarker

Abstract

S100B is a calcium-binding protein mainly concentrated in astrocytes in the nervous system. Its levels in biological fluids are recognized as a reliable biomarker of active neural distress, and more recently, mounting evidence points to S100B as a Damage-Associated Molecular Pattern molecule, which, at high concentration, triggers tissue reactions to damage. S100B levels and/or distribution in the nervous tissue of patients and/or experimental models of different neural disorders, for which the protein is used as a biomarker, are directly related to the progress of the disease. In addition, in experimental models of diseases such as Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic and vascular acute neural injury, epilepsy, and inflammatory bowel disease, alteration of S100B levels correlates with the occurrence of clinical and/or toxic parameters. In general, overexpression/administration of S100B worsens the clinical presentation, whereas deletion/inactivation of the protein contributes to the amelioration of the symptoms. Thus, the S100B protein may be proposed as a common pathogenic factor in different disorders, sharing different symptoms and etiologies but appearing to share some common pathogenic processes reasonably attributable to neuroinflammation.

Effects of Fisetin Treatment on Cellular Senescence of Various Tissues and Organs of Old Sheep

“…However, mounting evidence indicates that S100B serves as a Damage-Associated Molecular Pattern (DAMP) molecule, which at high concentrations can trigger tissue damage [ 48 ]. In many neurological disorders, S100B levels correlate with clinical or toxic parameters; thus, S100B can serve as a therapeutic target for neurological diseases [ 48 , 49 ]. These results further indicate the beneficial effects of fisetin for brain aging.…”

Periodic heat waves-induced neuronal etiology in the elderly is mediated by gut-liver-brain axis: a transcriptome profiling approach

“…The enriched pathways observed in the brain under heat stress strongly highlighted the activation of S100B signaling, a central nervous system calcium-binding protein concentrated in astrocytes, that serves as a reliable biomarker of neural distress and is implicated in neuropathology. In brain inflammation, the above molecule acts as both a pro-inflammatory cytokine and a Damage-Associated Molecular Pattern (DAMP), displaying concentration-dependent effects on neurons, ranging from neurotrophic support to inducing apoptosis 48 , 49 . Another pathway predicted in brain tissues of the heat stress group was the activation of Interleukin-17 (IL-17) signaling, which is associated with disrupting the blood–brain barrier, fostering neuroinflammation, and contributing to tissue damage in neuroinflammatory conditions of ischemic brain injury.…”

Cellular and Molecular Pathophysiology of Traumatic Brain Injury: What Have We Learned So Far?

“…Initially, it was discovered that this marker plays a fundamental role in the differentiation and development of astrocytes but also in the neurite outgrowth. However, as well as the dual face of glial scar, the S100B overexpression also possess two contradictory activities: On one hand, its overexpression is often associated with injury events, such as spinal cord injury, brain traumas and stroke, and it displays a deleterious activity [ 195 , 196 ]. On the other hand, this protein also negatively modulates the neuroinflammation by the TNF-α pathway and other pro-inflammatory mediators and also the reduction of microgliosis, depending on the S100B extracellular concentration [ 196 , 197 , 198 ].…”

“…However, as well as the dual face of glial scar, the S100B overexpression also possess two contradictory activities: On one hand, its overexpression is often associated with injury events, such as spinal cord injury, brain traumas and stroke, and it displays a deleterious activity [ 195 , 196 ]. On the other hand, this protein also negatively modulates the neuroinflammation by the TNF-α pathway and other pro-inflammatory mediators and also the reduction of microgliosis, depending on the S100B extracellular concentration [ 196 , 197 , 198 ]. Insulin-like growth factor (IGF) has several biological activities in the CNS related to the brain development and the synaptoplasticity.…”