Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia.
Nat Commun
; 4: 1562, 2013.
Article
en En
| MEDLINE
| ID: mdl-23463005
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Microglía
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Comunicación Paracrina
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Receptor Toll-Like 2
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Alfa-Sinucleína
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Neuronas
Límite:
Animals
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Humans
Idioma:
En
Año:
2013
Tipo del documento:
Article