| First Author | Kim C | Year | 2013 |
| Journal | Nat Commun | Volume | 4 |
| Pages | 1562 | PubMed ID | 23463005 |
| Mgi Jnum | J:347950 | Mgi Id | MGI:6839590 |
| Doi | 10.1038/ncomms2534 | Citation | Kim C, et al. (2013) Neuron-released oligomeric alpha-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nat Commun 4:1562 |
| abstractText | Abnormal aggregation of alpha-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 alpha-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 alpha-synuclein is conformation-sensitive; only specific types of oligomer can interact with and activate TLR2. This paracrine interaction between neuron-released oligomeric alpha-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. |
