{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:20:10Z","timestamp":1787754010408,"version":"build-2784847793"},"reference-count":51,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T00:00:00Z","timestamp":1753488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Clinical Research Center for Child Health and Disorders","award":["NCRCCHD-2022-GP-0X"],"award-info":[{"award-number":["NCRCCHD-2022-GP-0X"]}]},{"name":"National Clinical Research Center for Child Health and Disorders","award":["W0126"],"award-info":[{"award-number":["W0126"]}]},{"name":"National Clinical Research Center for Child Health and Disorders","award":["2024GDRC015"],"award-info":[{"award-number":["2024GDRC015"]}]},{"name":"Program for Youth Innovation in Future Medicine, Chongqing Medical University","award":["NCRCCHD-2022-GP-0X"],"award-info":[{"award-number":["NCRCCHD-2022-GP-0X"]}]},{"name":"Program for Youth Innovation in Future Medicine, Chongqing Medical University","award":["W0126"],"award-info":[{"award-number":["W0126"]}]},{"name":"Program for Youth Innovation in Future Medicine, Chongqing Medical University","award":["2024GDRC015"],"award-info":[{"award-number":["2024GDRC015"]}]},{"name":"Chongqing Municipal Science and Health Joint Medical Research Middle and Young Medical High-end Talent Project","award":["NCRCCHD-2022-GP-0X"],"award-info":[{"award-number":["NCRCCHD-2022-GP-0X"]}]},{"name":"Chongqing Municipal Science and Health Joint Medical Research Middle and Young Medical High-end Talent Project","award":["W0126"],"award-info":[{"award-number":["W0126"]}]},{"name":"Chongqing Municipal Science and Health Joint Medical Research Middle and Young Medical High-end Talent Project","award":["2024GDRC015"],"award-info":[{"award-number":["2024GDRC015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tuberous sclerosis complex (TSC) is a systemic disease caused by mutations in either the TSC1 (encoding hamartin) or TSC2 (encoding tuberin) gene, with mutations in the TSC2 gene potentially leading to more severe clinical symptoms. Neurological symptoms are a common clinical manifestation of TSC, and neuroinflammation is thought to play an important role. Glial cells are a major source of neuroinflammation, but whether microglia are involved in the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and the expression of interleukin-1\u03b2 (IL-1\u03b2) in TSC patients remains unclear. We used a transcriptome sequencing dataset for bioinformatics analysis to explore the differences in the expression of microglial inflammasome-associated hub genes. TSC2 knockdown (TSC2 KD) microglia (HMC3 cell line) were generated by lentivirus, and the expression of inflammasome-associated hub genes, microglial activation, and NLRP3 inflammasome activation were verified. In addition, experiments were performed to explore the regulatory effects of rapamycin. Bioinformatics analysis identified a total of eight inflammasome-associated hub genes. By detecting GFP fluorescence, TSC2 mRNA, TSC2 protein expression, and the phosphorylation of the mammalian target of rapamycin (p-mTOR)\/mTOR, we confirmed that the TSC2 KD microglia model was successfully established. Compared with the control group, the TSC2 KD group presented higher mRNA levels and fluorescence intensities of microglia AIF1 and CD68, as well as greater reactive oxygen species (ROS) production. Eight inflammasome-associated hub gene mRNA assays revealed that the expression of the NLRP3 and IL1B genes was increased. Compared with the control group, the TSC2 KD group presented increased levels of NLRP3 and Pro-IL-1\u03b2 proteins in cells and Cleaved-Caspase 1 and Cleaved-IL-1\u03b2 proteins in the supernatant, suggesting NLRP3 inflammasome activation. Rapamycin intervention alleviated these changes, demonstrating that the TSC2 gene regulation of microglial activation and NLRP3 inflammasome activation are correlated with mTOR phosphorylation. In conclusion, microglia are activated in TSC patients and participate in the NLRP3 inflammasome-associated neuroinflammatory response, and rapamycin treatment can alleviate these changes.<\/jats:p>","DOI":"10.3390\/ijms26157244","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T10:51:14Z","timestamp":1753699874000},"page":"7244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Activation of the Microglial NLRP3 Inflammasome Is Involved in Tuberous Sclerosis Complex-Related Neuroinflammation"],"prefix":"10.3390","volume":"26","author":[{"given":"Ran","family":"Ding","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Child Health and Disorders, Chongqing 400014, China"},{"name":"Department of Neurology, Children\u2019s Hospital of Chongqing Medical University, Chongqing 400014, China"},{"name":"Ministry of Education Key Laboratory of Child 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Children\u2019s Hospital of Chongqing Medical University, Chongqing 400014, China"},{"name":"Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China"},{"name":"Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing 400014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingman","family":"Wang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Child Health and Disorders, Chongqing 400014, China"},{"name":"Department of Neurology, Children\u2019s Hospital of Chongqing Medical University, Chongqing 400014, China"},{"name":"Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China"},{"name":"Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing 400014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyao","family":"Han","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Child Health and Disorders, Chongqing 400014, China"},{"name":"Department of Neurology, Children\u2019s Hospital of Chongqing Medical University, Chongqing 400014, China"},{"name":"Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China"},{"name":"Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing 400014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxiong","family":"Gui","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Child Health and Disorders, Chongqing 400014, China"},{"name":"Department of Neurology, Children\u2019s Hospital of Chongqing Medical University, Chongqing 400014, China"},{"name":"Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China"},{"name":"Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing 400014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Yang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Child Health and Disorders, Chongqing 400014, China"},{"name":"Department of Neurology, Children\u2019s Hospital of Chongqing Medical University, Chongqing 400014, China"},{"name":"Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China"},{"name":"Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing 400014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Cheng","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Child Health and Disorders, Chongqing 400014, China"},{"name":"Department of Neurology, Children\u2019s Hospital of Chongqing 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