{Reference Type}: Journal Article
{Title}: Involvement of insulin signalling pathway in methamphetamine-induced hyperphosphorylation of Tau.
{Author}: Xu H;Chen X;Wang J;Yang T;Liu N;Cheng J;Gao R;Liu J;Xiao H;
{Journal}: Toxicology
{Volume}: 408
{Issue}: 0
{Year}: 09 2018 1
{Factor}: 4.571
{DOI}: 10.1016/j.tox.2018.07.002
{Abstract}: Methamphetamine (METH), an amphetamine-like drug, is one of the most commonly used central nervous system psychostimulants worldwide. METH abuse frequently leads to cognitive decline and dementia-like changes, but the mechanisms remain poorly understood. In the present study, the mechanisms of METH-induced changes in Alzheimer's disease-like pathological protein in Neuro2A cells were explored. Our results indicated that METH exposure significantly increased the expression of the pathological protein hyperphosphorylated tau (p-tau). Further analysis revealed that METH exposure obviously disrupted insulin signalling, resulted in brain insulin resistance, which manifested as downregulation of the insulin receptor substrate-1, AKTser 473, and GSK3β activation. Notably, the linkage between p-tau expression and insulin signalling can be partially verified by treatment with the insulin-sensitizing drug rosiglitazone and GSK3β inhibitor TWS119 which specifically reversed METH-induced hyperphosphorylation of tau. Our results indicate that insulin signalling can be therapeutically exploited for attenuating METH-induced upregulation of p-tau.