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Int J Biol Sci 2023; 19(10):3249-3265. doi:10.7150/ijbs.81900 This issue Cite

Research Paper

β-amyloid binds to microglia Dectin-1 to induce inflammatory response in the pathogenesis of Alzheimer's disease

Xia Zhao1#, Jinfeng Sun1,2#, Li Xiong1, Lingyu She2, Liwei Li1, Hao Tang1, Yuqing Zeng1, Fan Chen1, Xue Han1, Shiju Ye3, Wei Wang1, Xu Wang3,4, Guang Liang1,3,✉

1. Affiliated Yongkang First People's Hospital and School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, 310012, China.
2. Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China.
3. Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang,325035, China.
4. Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health); Wenzhou Medical University, Wenzhou, Zhejiang,325035, China.
# Equal contribution

✉ Corresponding author: Guang Liang, Ph.D., Professor. Address: Affiliated Yongkang First People's Hospital and School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, 310012, China. E-mail: wzmcliangguangcom

Citation:
Zhao X, Sun J, Xiong L, She L, Li L, Tang H, Zeng Y, Chen F, Han X, Ye S, Wang W, Wang X, Liang G. β-amyloid binds to microglia Dectin-1 to induce inflammatory response in the pathogenesis of Alzheimer's disease. Int J Biol Sci 2023; 19(10):3249-3265. doi:10.7150/ijbs.81900. https://www.ijbs.com/v19p3249.htm
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Abstract

Graphic abstract

Microglia-mediated neuroinflammation is closely related to the development of Alzheimer's disease (AD). In the early stages of the inflammation response, pattern recognition receptors (PRRs) play a key role in clearing damaged cells and defending against infection by recognizing endogenous and exogenous ligands. However, the regulation of pathogenic microglial activation and its role in AD pathology remains poorly understood. Here we showed that a pattern recognition receptor called Dectin-1, expressed on microglia, mediates the pro-inflammatory responses of beta-amyloid (Aβ). Knockout of Dectin-1 reduced Aβ1-42 (Aβ42)-induced microglial activation, inflammatory responses, and synaptic and cognitive deficits in Aβ42-infused AD mice. Similar results were obtained in the BV2 cell model. Mechanistically, we showed that Aβ42 could directly bind to Dectin-1, causing Dectin-1 homodimerization and activating downstream spleen tyrosine kinase (Syk)/nuclear factor-κB (NF-κB) signaling pathway to induce the expression of inflammatory factors and, in turn, AD pathology. These results suggest the important role of microglia Dectin-1 as a new direct receptor for Aβ42 in microglial activation and AD pathology and provide a potential therapeutic strategy for neuroinflammation in AD.

Keywords: β-amyloid, Dectin-1, Microglia, Neuroinflammation, Alzheimer's disease

Citation styles

APA
Zhao, X., Sun, J., Xiong, L., She, L., Li, L., Tang, H., Zeng, Y., Chen, F., Han, X., Ye, S., Wang, W., Wang, X., Liang, G. (2023). β-amyloid binds to microglia Dectin-1 to induce inflammatory response in the pathogenesis of Alzheimer's disease. International Journal of Biological Sciences, 19(10), 3249-3265. https://doi.org/10.7150/ijbs.81900.

ACS
Zhao, X.; Sun, J.; Xiong, L.; She, L.; Li, L.; Tang, H.; Zeng, Y.; Chen, F.; Han, X.; Ye, S.; Wang, W.; Wang, X.; Liang, G. β-amyloid binds to microglia Dectin-1 to induce inflammatory response in the pathogenesis of Alzheimer's disease. Int. J. Biol. Sci. 2023, 19 (10), 3249-3265. DOI: 10.7150/ijbs.81900.

NLM
Zhao X, Sun J, Xiong L, She L, Li L, Tang H, Zeng Y, Chen F, Han X, Ye S, Wang W, Wang X, Liang G. β-amyloid binds to microglia Dectin-1 to induce inflammatory response in the pathogenesis of Alzheimer's disease. Int J Biol Sci 2023; 19(10):3249-3265. doi:10.7150/ijbs.81900. https://www.ijbs.com/v19p3249.htm

CSE
Zhao X, Sun J, Xiong L, She L, Li L, Tang H, Zeng Y, Chen F, Han X, Ye S, Wang W, Wang X, Liang G. 2023. β-amyloid binds to microglia Dectin-1 to induce inflammatory response in the pathogenesis of Alzheimer's disease. Int J Biol Sci. 19(10):3249-3265.

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