Methamphetamine exposure induces neuropathic protein β-Amyloid expression.

Methamphetamine (METH) abusing contributes to dopaminergic neurons degeneration, resulting inParkinson's disease (PD)-like changes. More recently, the association between METH exposure and the Alzheimer's disease (AD)-like changes gained more attention, however, the underlying mechanisms remain poorly understood. In the present study, we aimed to investigate whether METH exposure promotes the formation of Aβ42, one of the key AD-like pathological proteins. With the cell model PC-12 cell line, it showed that METH treatment significantly increased the level of the precursor protein APP and its hydrolysates CTFs expression in a dose-dependent manner. In parallel, with the ELISA assay, we found that METH exposure contributed to an obvious elevation of the Aβ1-42 excretion in the cell culture supernatant. Therefore, we examined the expression of p-GSK3α and BACE-1, which were responsible for APP and Aβ1-42 generation respectively, it suggested in that METH obviously activated the p-GSK3α and increased the level of BACE-1, and the expression of BACE-1 was also detected by the immunofluorescence, with the significant elevation of the BACE-1 fluorescence intensity. In conclusion, METH treatment promotes the expression of Aβ precursor protein APP and its hydrolysis product CTFs and Aβ1-42, and p-GSK3α as well as BACE-1 may be involved in this process.