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Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia

Nature communications, 2013, Vol.4 (1), p.1562-1562, Article 1562 [Peer Reviewed Journal]

ISSN: 2041-1723 ;EISSN: 2041-1723 ;DOI: 10.1038/ncomms2534 ;PMID: 23463005

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Title:
Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia
Author: Kim, Changyoun ; Ho, Dong-Hwan ; Suk, Ji-Eun ; You, Sungyong ; Michael, Sarah ; Kang, Junghee ; Joong Lee, Sung ; Masliah, Eliezer ; Hwang, Daehee ; Lee, He-Jin ; Lee, Seung-Jae
Subjects: alpha-Synuclein - chemistry ; alpha-Synuclein - metabolism ; Animals ; Cells, Cultured ; Chemokines - metabolism ; Chromatography, Gel ; Dopaminergic Neurons - metabolism ; Humans ; Immunohistochemistry ; Lewy Body Disease - metabolism ; Lewy Body Disease - pathology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microglia - metabolism ; Microglia - pathology ; Neurons - metabolism ; Paracrine Communication ; Protein Conformation ; Protein Structure, Quaternary ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 2 - agonists ; Toll-Like Receptor 2 - chemistry ; Toll-Like Receptor 2 - metabolism ; Up-Regulation
Is Part Of: Nature communications, 2013, Vol.4 (1), p.1562-1562, Article 1562
Description: Abnormal aggregation of α-synuclein and sustained microglial activation are important contributors to the pathogenic processes of Parkinson's disease. However, the relationship between disease-associated protein aggregation and microglia-mediated neuroinflammation remains unknown. Here, using a combination of in silico, in vitro and in vivo approaches, we show that extracellular α-synuclein released from neuronal cells is an endogenous agonist for Toll-like receptor 2 (TLR2), which activates inflammatory responses in microglia. The TLR2 ligand activity of α-synuclein is conformation-sensitive; only specific types of oligomer can interact with and activate TLR2. This paracrine interaction between neuron-released oligomeric α-synuclein and TLR2 in microglia suggests that both of these proteins are novel therapeutic targets for modification of neuroinflammation in Parkinson's disease and related neurological diseases.
Publisher: England
Language: English
Identifier: ISSN: 2041-1723
EISSN: 2041-1723
DOI: 10.1038/ncomms2534
PMID: 23463005
Source: MEDLINE
PubMed Central
ProQuest Central

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Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia

ISSN: 2041-1723 ;EISSN: 2041-1723 ;DOI: 10.1038/ncomms2534 ;PMID: 23463005

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