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

Author

Listed:
  • Changyoun Kim

    (Konkuk University
    SMART-IABS, Konkuk University)

  • Dong-Hwan Ho

    (Konkuk University
    SMART-IABS, Konkuk University)

  • Ji-Eun Suk

    (Konkuk University
    SMART-IABS, 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
    School of Medicine, Konkuk University)

  • Seung-Jae Lee

    (Konkuk University
    SMART-IABS, Konkuk University)

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.

Suggested Citation

  • Changyoun Kim & Dong-Hwan Ho & Ji-Eun Suk & Sungyong You & Sarah Michael & Junghee Kang & Sung Joong Lee & Eliezer Masliah & Daehee Hwang & He-Jin Lee & Seung-Jae Lee, 2013. "Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia," Nature Communications, Nature, vol. 4(1), pages 1-12, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2534
    DOI: 10.1038/ncomms2534
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    Cited by:

    1. Rhonda L. McFleder & Anastasiia Makhotkina & Janos Groh & Ursula Keber & Fabian Imdahl & Josefina Peña Mosca & Alina Peteranderl & Jingjing Wu & Sawako Tabuchi & Jan Hoffmann & Ann-Kathrin Karl & Axel, 2023. "Brain-to-gut trafficking of alpha-synuclein by CD11c+ cells in a mouse model of Parkinson’s disease," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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