| First Author | Rannikko EH | Year | 2015 |
| Journal | BMC Neurosci | Volume | 16 |
| Pages | 57 | PubMed ID | 26346361 |
| Mgi Jnum | J:318321 | Mgi Id | MGI:6859199 |
| Doi | 10.1186/s12868-015-0192-0 | Citation | Rannikko EH, et al. (2015) Exogenous alpha-synuclein induces toll-like receptor 4 dependent inflammatory responses in astrocytes. BMC Neurosci 16:57 |
| abstractText | BACKGROUND: The pathological hallmarks of Parkinson's disease are intracellular inclusions composed mainly of misfolded alpha-synuclein (alphaSYN). Under physiological conditions alphaSYN is mostly localized in synapses. In addition, a portion of alphaSYN is secreted to the extracellular space, where it may be sequestered by neighboring cells and could induce inflammatory responses. The mechanisms of alphaSYN internalization and signal transduction are not unequivocally clarified. In this work we investigated in primary mouse astrocytes the involvement of toll-like receptor 4 (TLR4) in the induction of inflammatory responses upon exposure to purified human alphaSYN produced in bacteria. RESULTS: The mRNA induction of pro-inflammatory cytokines, inducible nitric oxide synthase and cyclooxygenase-2 was significantly reduced in TLR4 knockout astrocytes. The alphaSYN-mediated activation of c-Jun N-terminal kinases and p38 mitogen-activated protein kinase tended to be diminished, and nuclear translocation of the p65 subunit of nuclear factor kappaB was abolished in TLR4 knockout astrocytes. In contrast, the uptake of exogenous alphaSYN was unaffected by TLR4 knockout. CONCLUSIONS: Extracellular alphaSYN can activate pro-inflammatory TLR4 pathways in astrocytes, whereas alphaSYN uptake is independent of TLR4. |
