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 A beta(42), 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 A beta(42) excretion in the cell culture supernatant. Therefore, we examined the expression of p-GSK3 alpha and BACE-1, which were responsible for APP and A beta(42) generation respectively, it suggested in that METH obviously activated the p-GSK3 alpha 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 A beta precursor protein APP and its hydrolysis product CTFs and A beta(1-42), and p-GSK3 alpha as well as BACE-1 may be involved in this process.