Bibliographic Details
| Title: |
Inhibiting NLRP3 Inflammasome Activation by CY-09 Helps to Restore Cerebral Glucose Metabolism in 3×Tg-AD Mice |
| Authors: |
Shuangxue Han, Zhijun He, Xia Hu, Xiaoqian Li, Kaixin Zheng, Yingying Huang, Peng Xiao, Qingguo Xie, Jiazuan Ni, Qiong Liu |
| Source: |
Antioxidants, Vol 12, Iss 3, p 722 (2023) |
| Publisher Information: |
MDPI AG, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Therapeutics. Pharmacology |
| Subject Terms: |
Alzheimer’s disease, glucose metabolism, NLRP3 inflammasome, insulin resistance, oxidative stress, CY-09, Therapeutics. Pharmacology, RM1-950 |
| More Details: |
The reduction of the cerebral glucose metabolism is closely related to the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in Alzheimer’s disease (AD); however, its underlying mechanism remains unclear. In this paper, 18F-flurodeoxyglucose positron emission tomography was used to trace cerebral glucose metabolism in vivo, along with Western blotting and immunofluorescence assays to examine the expression and distribution of associated proteins. Glucose and insulin tolerance tests were carried out to detect insulin resistance, and the Morris water maze was used to test the spatial learning and memory ability of the mice. The results show increased NLRP3 inflammasome activation, elevated insulin resistance, and decreased glucose metabolism in 3×Tg-AD mice. Inhibiting NLRP3 inflammasome activation using CY-09, a specific inhibitor for NLRP3, may restore cerebral glucose metabolism by increasing the expression and distribution of glucose transporters and enzymes and attenuating insulin resistance in AD mice. Moreover, CY-09 helps to improve AD pathology and relieve cognitive impairment in these mice. Although CY-09 has no significant effect on ferroptosis, it can effectively reduce fatty acid synthesis and lipid peroxidation. These findings provide new evidence for NLRP3 inflammasome as a therapeutic target for AD, suggesting that CY-09 may be a potential drug for the treatment of this disease. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2076-3921 |
| Relation: |
https://www.mdpi.com/2076-3921/12/3/722; https://doaj.org/toc/2076-3921 |
| DOI: |
10.3390/antiox12030722 |
| Access URL: |
https://doaj.org/article/1a0c54f39917419f8e3c0d3215af5a44 |
| Accession Number: |
edsdoj.1a0c54f39917419f8e3c0d3215af5a44 |
| Database: |
Directory of Open Access Journals |
