High Glucose Aggravates Cerebral Ischemia/Reperfusion via Truncated <scp>NLRP3</scp> ‐Mediated Hexokinase‐2 Translocation
Our study elucidates PKA-mediated generation of a 30 kD N-terminal truncation of NLRP3 (miniNLRP3) in a serine protease-dependent manner, which could potentiate the activation of the NLRP3 inflammasome under high glucose conditions via promoting the dissociation of HK2 from mitochondria. These findings add a new dimension to our understanding of NLRP3 regulation in the context of stroke injury, and suggest that the PKA-miniNLRP3-HK2-NLRP3 pathway is a promising therapeutic strategy to improve stroke outcomes in patients with elevated blood glucose levels.
Authors
- Yongzhi Huang (ORCID: https://orcid.org/0000-0002-2503-1589)
- Lijuan Song (ORCID: https://orcid.org/0000-0002-5628-3180)
- Hengchang Zhang
- Ruoyi Guo (ORCID: https://orcid.org/0000-0002-7901-8427)
- Yang Zhang (ORCID: https://orcid.org/0000-0001-9674-4052)
- Zengqiang Yuan (ORCID: https://orcid.org/0000-0001-5739-2867)
- Xiang Li (ORCID: https://orcid.org/0000-0002-4239-3733)
- Junjie Wang (ORCID: https://orcid.org/0000-0002-5786-0146)
- Yajin Liao (ORCID: https://orcid.org/0000-0001-7067-0497)
- Lu‐Jun Zhou
Institutions
- Hebei Medical University (CN)
- State Administration of Traditional Chinese Medicine of the People's Republic of China (CN)
- ShenZhen People’s Hospital (CN)
- Chinese Institute for Brain Research (CN)
- University of South China (CN)
Publication Details
- Journal
- CNS Neuroscience & Therapeutics
- Published
- 2025-11-01
- DOI
- https://doi.org/10.1111/cns.70660
- Primary Topic
- Inflammasome and immune disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Hunan Province
- University of South China