The Wnt/β-catenin signaling pathway affects the distribution of cytoskeletal proteins in Aβ treated PC12 cells

Abstract

Alzheimer’s disease is pathologically characterized by the presence of senile plaques and neurofibrillary tangles in the central nervous system. Amyloid β-protein is toxic to neurons and induces phosphorylation of Tau protein, which accumulates in paired helical filaments and leads to the formation of neurofibrillary tangles. This study is focused on the Wnt/β-catenin pathway influence on Tau phosphorylation and the distribution of microtubules and neurofilaments in adrenal pheochromocytoma cells. It was found that neurofilament heavy polypeptide and microtubule-associated protein-2 aggregated after treatment with Aβ1-42. Treatment with Wnt5a reduced this aggregation, while Dickkopf-1 treatment promoted microtubule and neurofilament aggregation. Furthermore, Tau phosphorylation at Ser396, Ser422, and Ser199 was significantly reduced after Wnt5a treatment, whereas Dickkopf-1 increased the level of phosphorylation. These results suggest that the Wnt/β-catenin pathway influences the distribution of microtubules and neurofilaments, possibly by modulating the phosphorylation of Tau protein in adrenal pheochromocytoma cells.

Keywords

• |alzheimer’s disease|amyloid β-protein|wnt/β-catenin signaling pathway|tau phosphorylation