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

Changyoun Kim, Dong-Hwan Ho, Ji-Eun Suk, Sungyong You, Sarah Michael, Junghee Kang, Sung Joong Lee, Eliezer Masliah, Daehee Hwang, He-Jin Lee and Seung-Jae Lee ()
Additional contact information
Changyoun Kim: Konkuk University
Dong-Hwan Ho: Konkuk University
Ji-Eun Suk: Konkuk University
Sungyong You: School of Interdisciplinary Bioscience and Bioengineering, POSTECH
Sarah Michael: School of Medicine, University of California San Diego
Junghee Kang: School of Dentistry and Dental Research Institute, and Interdisciplinary Program in Genetic Engineering, Seoul National University
Sung Joong Lee: School of Dentistry and Dental Research Institute, and Interdisciplinary Program in Genetic Engineering, Seoul National University
Eliezer Masliah: School of Medicine, University of California San Diego
Daehee Hwang: School of Interdisciplinary Bioscience and Bioengineering, POSTECH
He-Jin Lee: SMART-IABS, Konkuk University
Seung-Jae Lee: Konkuk University

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: Abstract 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.

Date: 2013
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms2534 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2534

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms2534

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().