Targeting S100B in Cerebral Ischemia and in Alzheimer's Disease

Figure 4

Diagrammatic representation of brain amyloid-𝛽 (A𝛽) production/clearance, the harmful actions of S100B on A𝛽 production, and resultant effects on brain and plasma A𝛽 levels. In the amyloidogenic pathway, A𝛽 is primarily produced in neurons from sequential endoproteolytic cleavage of the type 1 transmembrane glycoprotein, 𝛽-amyloid precursor protein (APP), by 𝛽- and 𝛾-secretases. Subsequently, soluble A𝛽 is secreted into the extracellular space, and then enters into a dynamic equilibrium between soluble and deposited (insoluble, 𝛽-amyloid plaque) forms. Continual transport of soluble A𝛽 occurs into and from the plasma. S100B enhancement of 𝛽-secretase activity promotes A𝛽 production, resulting in higher soluble and deposited A𝛽 in the brain. In addition, S100B promotes a damaging glial cytokine cycle through activation of astrocytes and microglia, resulting in enhancement of the amyloidogenic pathway.