Methamphetamine exposure upregulates the amyloid precursor protein and hyperphosphorylated tau expression: The roles of insulin signaling in SH-SY5Y cell line

Methamphetamine (METH) is a potent and highly addictive central nervous system stimulant. The association between METH exposure and Alzheimer's disease (AD) has gained more attention, but, the mechanisms behind METH-induced neuron-related adverse outcomes remain poorly understood. With the western blot assay, our results revealed that METH exposure significantly increased the expression of AD-associated pathological proteins, including the amyloid precursor protein (APP) and the phosphorylated tau protein (p-tau). Meanwhile, the insulin signaling was disturbed after the administration of METH, since the key insulin signaling proteins, such as p-AKT, p-GSK3 alpha, p-GSK3 beta and p-ERK, were reduced. Additionally, the linking between the pathological proteins and the insulin signaling mediated by METH in the present work was verified by the treatment with the insulin signaling enhancer rosiglitazone, which was shown to improve the insulin signaling and decrease APP and p-tau expression. Thus, targeting insulin signaling may provide novel insights into potential therapeutic intervention for METH-mediated AD-like neurodegeneration.