Methamphetamine (METH), a powerful psychoactive drug, causes damage to the nervous system and leads to degenerative changes similar to Alzheimer's disease (AD), however, the molecular mechanism between the toxicity of METH and AD-related symptoms remains poorly understood. In this study, we investigated the effect of METH exposure on the accumulation of amyloid-β by establishing the animal and cell models. The results showed that METH exposure increased amyloid precursor protein (APP) and β-secretase (BACE1), contributed to the accumulation of amyloid-β, and which was alleviated with the pretreatment of BACE1 inhibitor. In addition, METH exposure decreased ubiquitin carboxy-terminal hydrolases L1 (UCHL1) which was related to the degradation of BACE1, and therefore led to the up-regulation of BACE1. In summary, the study could provide a new insight into the molecular mechanisms of METH toxicity and new evidence for the link between METH abuse and AD.

甲基苯丙胺 (METH) 是一种强大的精神活性药物，会对神经系统造成损害并导致类似于阿尔茨海默病 (AD) 的退行性变化，然而，甲基苯丙胺的毒性与 AD 相关症状之间的分子机制仍知之甚少。在这项研究中，我们通过建立动物和细胞模型研究了 METH 暴露对淀粉样蛋白-β 积累的影响。结果表明，METH 暴露增加了淀粉样蛋白前体蛋白 (APP) 和 β-分泌酶 (BACE1)，有助于淀粉样蛋白-β 的积累，并且通过 BACE1 抑制剂的预处理得到缓解。此外，METH 暴露降低了泛素羧基末端水解酶 L1 (UCHL1)，这与 BACE1 的降解有关，因此导致 BACE1 的上调。总之，