Metformin inhibits Aβ25-35 -induced apoptotic cell death in SH-SY5Y cells.

Metformin, a first-line drug for type-2 diabetes, plays a potentially protective role in preventing Alzheimer's disease (AD), but its underlying mechanism is unclear. In this study, Aβ25-35 -treated SH-SY5Y cells were used as a cell model of AD to investigate the neuroprotective effect of metformin, as well as its underlying mechanisms. We found that metformin decreased the cell apoptosis rate and death, ratio of Bcl-2/Bax, and expression of NR2A and NR2B, and increased the expression of LC3 in Aβ25-35 -treated SH-SY5Y cells. Metformin also reduced intracellular and extracellular Glu concentrations, as well as the intracellular concentration of Ca2+ and ROS in Aβ25-35 -treated SH-SY5Y cells. These findings suggest that metformin inhibits Aβ25-35 -treated SH-SY5Y cell death by inhibiting apoptosis, decreasing intracellular Ca2+ and ROS by reducing neurotoxicity of excitatory amino acids, and by possibly reversing autophagy disorder via regulating autophagy process.