Ginkgolide B inhibits NLRP3 inflammasome activation and promotes microglial M2 polarization in Aβ1-42-induced microglia cells.

Abstract

Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome-mediated chronic neuroinflammation plays a crucial role in the progression of Alzheimer's disease (AD), which is related to microglial activation. Using quantitative proteomic analysis, we identified 25 up-regulated and 83 down-regulated proteins in amyloid beta (Aβ)1-42-induced BV2 cells. Among the differentiallyexpressedproteins involved in inflammation, the NLRP3 protein level increased dramatically. Ginkgolide B (GB) prevents Aβ-induced neuroinflammation and neurotoxic effects in multiple neurodegenerative disorders. However, its role in NLRP3 inflammasome-mediated neuroinflammation in AD remain unknown. We found that GB treatment ameliorated Aβ1-42-induced pathological damages and inhibited NLRP3 inflammasome activation. Furthermore, GB enhanced the expression of M2 microglial markers and suppressed the expression of M1 microglial markers. Our findings suggest that GB treatment prevents the pathological processes of AD and suppresses neuroinflammation by inhibiting NLRP3 inflammasome activation and promoting microglial M2 polarization.

• Authors: Yidan Zhang, Yuan Zhao, Jian Zhang, Ya Gao, Shuyue Li, Cui Chang, Donghua Yu, Guofeng Yang
• Journal: Neuroscience letters (Neurosci Lett) Vol. 764 Pg. 136206 (11 01 2021) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 34478813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Ginkgolides
• Inflammasomes
• Lactones
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Peptide Fragments
• amyloid beta-protein (1-42)
• ginkgolide B

Topics

• Alzheimer Disease (drug therapy, immunology, pathology)
• Amyloid beta-Peptides (metabolism)
• Animals
• Disease Models, Animal
• Ginkgolides (pharmacology, therapeutic use)
• Humans
• Inflammasomes (antagonists & inhibitors, immunology, metabolism)
• Lactones (pharmacology, therapeutic use)
• Mice
• Microglia (drug effects, immunology, pathology)
• NLR Family, Pyrin Domain-Containing 3 Protein (antagonists & inhibitors, metabolism)
• Neuroinflammatory Diseases (drug therapy, immunology, pathology)
• Peptide Fragments (metabolism)