Fig. 2

Phosphoinositides signaling cascade in Alzheimer’s disease. In AD condition, amyloid-beta known to down regulate the production of PI 4,5-P2 via SHIP-2 related mechanism. The PI 3,4,5-P3 species is increasingly hydrolyzed to PI 3,4-P2, which in turn enhances the pathway of Tau phosphorylation via GSK-3β-associated mechanism that impose neuronal death and neurodegeneration. Aβ-induced elevated concentration of PI-PLC hydrolyzes PI 4,5-P2 into IP3 and DAG which initiated Ras dependent ERK activation that eventually increases neurodegeneration. Aβ largely inhibits PI3K activity, a key player of Akt-a cell survival pathway. The reduced level of PI 4, 5-P2 down regulate the actin polymerization and phagocytosis hence there is impairment in the clearance of Aβ and increases in formation of phospho-Tau