S100A1 Mediated Signaling in the Nervous System

S100 proteins are a large family of Ca2 binding protein that have been implicated in the onset and progression of neurological diseases such as Alzheimer’s disease (AD), cancer, and multiple sclerosis. However, the molecular mechanisms of altered S100 signaling in these diseases have not been elucidated. Recent studies from our laboratory demonstrate that one member of the family, S100A1, regulates amyloid precursor protein (APP) production and glycogen synthase kinase 3β (GSK3β) signaling in neuronal cell lines. In the brain, APP and GSK3β are involved in the development of senile plaques and tangles seen in AD and other dementias. However, neuronal cell lines do not faithfully mimic the diverse cell types/subtypes and complex anatomical organization of the intact brain. Therefore, this project uses a genetic approach to determine if S100A1 regulates amyloid precursor protein and GSK3β expression in the in vivo brain. S100A1-/- and wildtype levels for APP are 0.58 ± 0.10 vs. 0.46 ± 0.07 and for phospho-GSK3β are 0.22 ± 0.07 vs. 0.27± 0.06. However, these differences are not statistically significant. Thus, our study demonstrates that S100A1 does not regulate the in vivo levels of APP or GSK3β