Skip to Main content Skip to Navigation
New interface
Journal articles

Microglial NLRP3 inflammasome activation upon TLR2 and TLR5 ligation by distinct $\alpha$-synuclein assemblies

Abstract : Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder characterized by the formation of cellular inclusions inside neurons that are rich in an abnormal form of the protein $\alpha$-synuclein ($\alpha$-syn). Microglia are the CNS resident immune cells that react to misfolded proteins through pattern recognition receptor ligation and activation of signaling transduction pathways. Here, we studied microglial activation by distinct $\alpha$-syn forms and their clearance. Internalization of $\alpha$-syn monomers and oligomers efficiently activated the NLRP3 inflammasome via Toll-like receptor-2 and -5 ligation, thereby acting on different signaling checkpoints. We found that primary microglia effectively engulf $\alpha$-syn, but hesitate in its degradation. NLRP3 inhibition by the selective inhibitor CRID3 and NLRP3 deficiency improved the overall clearance of $\alpha$-syn oligomers. Together, these data show that distinct $\alpha$-syn forms exert different microglial NLRP3 inflammasome activation properties, thereby compromising its degradation which can be prevented by NLRP3 inhibition.
Document type :
Journal articles
Complete list of metadata
Contributor : Ronald Melki Connect in order to contact the contributor
Submitted on : Thursday, September 16, 2021 - 2:25:02 PM
Last modification on : Sunday, June 26, 2022 - 3:13:35 AM
Long-term archiving on: : Friday, December 17, 2021 - 6:02:39 PM


Files produced by the author(s)



Hannah Scheiblich, Luc Bousset, Stephanie Schwartz, Angelika Griep, Eicke Latz, et al.. Microglial NLRP3 inflammasome activation upon TLR2 and TLR5 ligation by distinct $\alpha$-synuclein assemblies. Journal of Immunology, In press, ⟨10.4049/jimmunol.2100035⟩. ⟨cea-03344484⟩



Record views


Files downloads