Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by memory loss. Our recent study has demonstrated that thioredoxin-1 (Trx-1) could protect neurons via repressing NLRP1âmediated neuronal pyroptosis in AD models. However, whether Trx-1 could inhibit NLRP3 activation is largely unknown. Here, we found that AAV-mediated Trx-1 overexpression significantly inhibited NLRP3-mediated pyroptosis in the hippocampus of APP/PS1 mice. A mouse hippocampal neuron HT22 cell line overexpressing Trx-1 was successfully obtained through lentivirus transfection. Further study showed that Trx-1 overexpression protected HT22 cells against the neurocytotoxicity of Aβ(25-35). Consistently with the results of in vivo experiments, overexpression of Trx-1 remarkedly inhibited the activation of NLRP3. In the contrary, knockdown of Trx-1 by siRNA transfection further aggravated the activation of NLRP3. Mechanistically, Trx-1 overexpression significantly inhibited the increase of thioredoxin-interacting protein (TXNIP) in in vivo and in vitro and weakened the interaction between TXNIP and NLRP3. Taken together, Trx-1 inhibits NLRP3-mediated pyroptosis by regulating TXNIP expression and its interaction with NLRP3 in AD models.
Thioredoxin-1 inhibits NLRP3-mediated pyroptosis by regulating TXNIP in models of Alzheimer's disease.
在阿尔茨海默病模型中,硫氧还蛋白-1通过调节TXNIP抑制NLRP3介导的细胞焦亡
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作者:Jia Jinjing, Sheng Zixuan, Zhang Yuqian, Guo Lunxi, Chen Zhuo'er, Zhu Dongsheng, Zeng Xiansi, Liu Hongjun
| 期刊: | Scientific Reports | 影响因子: | 3.900 |
| 时间: | 2025 | 起止号: | 2025 May 13; 15(1):16551 |
| doi: | 10.1038/s41598-025-01636-5 | 研究方向: | 细胞生物学 |
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