云南滥用毒品人数逐年增加，毒品滥用群体常伴HIV高发。研究表明，甲基苯丙胺(Meth)可显著增加HIV感染者神经症状及HIV痴呆发生率，二者对神经系统损伤具有协同作用。我们及其他人的研究发现，Meth与HIV-1Tat蛋白可通过氧化应激协同诱导神经元发生自噬。自噬过程由多种蛋白形成的自噬复合物进行调控。我们数据表明，Meth与HIV-1Tat蛋白均可上调内质网三结构域家族蛋白TRIM13和自噬相关蛋白ATG5/7水平启动自噬，但相互作用机制不清楚。本研究以树鼩为研究对象，从在体和离体水平明确Meth与HIV-1Tat蛋白是否可以通过氧化应激触发TRIM13蛋白上调，募集ULK1、Beclin1复合物与ATG5/7发生相互作用，进而与LC3结合启动自噬途径，并阐明上述途径在两者协同诱导多巴胺能神经元自噬中的作用。项目开展为新型毒品神经损伤机制提供新思路，为毒品滥用HIV感染者防治提供新策略。

The number of people with drug abuse increases every year in Yunnan, and drug abusers are at high risk of HIV. Methamphetamine (Meth) can significantly increase the incidence of HIV-associated neurological symptoms and AIDS dementia, which have synergistic damage to the nervous system. Our findings and recent studies indicate that Meth and HIV-1tat protein can synergistic induce neuronal autophagy through oxidative stress. Autophagy is regulated by autophagy complexes formed by multiple proteins. TRIM13 is a member of the family protein of tripartite motif in endoplasmic reticulum and participates in autophagy pathway. Our previous studies found that Meth and HIV-1tat protein could up-regulate TRIM13 protein and autophagy related protein ATG5/ATG7 to initiate the autophagy pathway, but the mechanisms of protein interaction are still unclear. Therefore, we investigate in vivo and in vitro study on dopaminergic neuron or using tree shrews to elucidate whether Meth and HIV-1Tat protein can trigger the up-regulation of TRIM13 protein through oxidative stress, and whether it can recruit ULK1 and Beclin1 complexes to interact with ATG5/ATG7, then bind with LC3 to initiate the autophagy pathway. This study will provide new ideas for exploring the mechanism of nerve injury induced by new drugs and novel targets for the prevention and treatment of drug abuse with HIV infection.