甲基苯丙胺（METH）滥用对中枢神经系统造成严重损害。有研究显示METH能导致神经元自噬，并进一步介导神经元凋亡，但其确切机制仍不清楚。我们前期预实验发现DNA损伤诱导转录因子4（DDIT4）在METH处理后表达显著升高，下调DDIT4表达后能降低神经细胞自噬的发生。提示我们，DDIT4可能在METH诱导神经细胞自噬中起重要作用。本研究拟采用分子生物学、细胞生物学及神经生物学等研究方法和手段确定①DDIT4在METH导致的神经细胞自噬中起重要作用；②DDIT4通过mTOR信号通路调控METH致神经细胞自噬。③METH诱导DDIT4经TSC或其他途径调控mTOR。通过本研究阐明DDIT4-mTOR信号轴在METH致神经细胞自噬中的作用，并为METH新型解毒药物提供新的策略和靶点。

The abuse of Methamphetamine (METH) has serious damage to the central nervous system. Previous studies have indicated that METH can induce neuronal autophagy, which result to neuronal apoptosis. However, the detail mechanism underlying of this is still unclear. In our preliminary study, we found that the expression of DNA-damage-inducible transcript 4 (DDIT4) was significantly increased after METH exposure in vivo and in vitro. Furthermore, the marker genes of autophagy were decreased following by DDIT4 silencing. These results suggested that DDIT4 may contribute to METH-induced autophagy. In this project, we will employ series of methods and technologies, including Molecular biology, cell biology, neurobiology methods and so on, and reach the end as below: ①Identify the key role of DDIT4 in METH-induced autophagy. ②Clarify whether DDIT4 mediated neuronal autophagy induced by METH via mTOR pathway. ③Explore whether DDIT4 blocked phosphorylated mTOR through TSC complex in METH-exposed neuron. The research will not only reveal the mechanism of DDIT4-mTOR signaling axis in the METH-induced neurotoxicity, but also is expected to offer new strategy and target for developing new drugs for protection from the METH-induced neurotoxicity.