| First Author | Zhao X | Year | 2023 |
| Journal | Int J Biol Sci | Volume | 19 |
| Issue | 10 | Pages | 3249-3265 |
| PubMed ID | 37416769 | Mgi Jnum | J:348464 |
| Mgi Id | MGI:7506030 | Doi | 10.7150/ijbs.81900 |
| Citation | Zhao X, et al. (2023) beta-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 |
| abstractText | 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 (Abeta). Knockout of Dectin-1 reduced Abeta1-42 (Abeta(42))-induced microglial activation, inflammatory responses, and synaptic and cognitive deficits in Abeta(42)-infused AD mice. Similar results were obtained in the BV2 cell model. Mechanistically, we showed that Abeta(42) could directly bind to Dectin-1, causing Dectin-1 homodimerization and activating downstream spleen tyrosine kinase (Syk)/nuclear factor-kappaB (NF-kappaB) 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 Abeta(42) in microglial activation and AD pathology and provide a potential therapeutic strategy for neuroinflammation in AD. |
