AGER and Cowden syndrome 1: S100B is a Ca2+-binding protein that, at higher concentrations, upregulates Interleukin-1β and Tumor Necrosis Factor α expression and activates the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB) via the receptor for advanced glycation end products (RAGE) in microglia and astrocytes [17,18], all of which are involved in CS progression and maintenance [8].