Methamphetamine and HIV-1 Tat Synergistically Induce Microglial Pyroptosis Via Activation of the AIM2 Inflammasome

• DOI: 10.1007/s10753-025-02266-9
• Publication Date: 2025-02-19T10:34:19Z
• Authors: Lin Miao; Haowei Wang; Xue Yang; Lisha Xu; Ruike Xu; Hanxin Teng; Yue Zhang; Yingjie Zhao; Genmeng Yang; Xiaofeng Zeng
• Keywords: Pyroptosis; AIM2

Abstract Objective Human immunodeficiency virus (HIV)-infected individuals who abuse methamphetamine (METH) exhibit more severe neurotoxicity and cognitive impairment. Pyroptosis, a programmed cell death pathway mediated by the inflammasome, has been implicated in various neurological diseases. This study aimed to elucidate role of AIM2 inflammasome METH- HIV-1 Tat-induced pyroptosis human brain tissue vitro models. Methods Postmortem from HIV-infected with history METH was analyzed for markers components using immunohistochemistry, immunofluorescence, Western blotting. BV2 microglial cells were lentivirally transduced knockdown expression. DNA damage assessed blotting comet assay. Expression pyroptosis-related proteins evaluated electron microscopy, blotting, immunofluorescence. Cell viability measured CCK8 Results Elevated levels observed users. Tat synergistically induced time- concentration-dependent manner, accompanied activation inflammasome. Knockdown significantly reduced expression proteins. Conclusion induce activating through dsDNA damage. These findings suggest that targeting may be promising therapeutic strategy HIV-associated neurocognitive disorder (HAND). Graphical abstract