Alpha-synuclein release by neurons activates the inflammatory response in a microglial cell line.
The neurodegenerative process in Parkinson's disease (PD) is accompanied by the presence of a neuroinflammatory response, which has been suggested as one of the principal components involved in PD progression. In this report we assessed the inflammatory potential of alpha-synuclein, a protein central to PD pathogenesis, released by neurons on the mouse microglia cell line BV-2. BV-2 cells were treated with conditioned medium isolated from normal SH-SY5Y cells and clones that over-express WT or mutant A53T alpha-synuclein. Conditioned medium isolated from over-expressing clones induced the transcription and release of pro-inflammatory cytokines. Treatment of SH-SY5Y alpha-synuclein over-expressing cells with MPP+, the active metabolite of the neurotoxin MPTP, increased the inflammatory response in BV-2 cells. In contrast, the direct exposure of BV-2 cells to MPP+ failed to induce an inflammatory response. These results support the hypothesis that WT and A53T alpha-synuclein has an important role in the initiation and maintenance of inflammation in PD, through the activation of a pro-inflammatory response in microglial cells.
Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK. l.alvarez@medsch.ucl.ac.uk
Lydia
L
Alvarez-Erviti
Yvonne
Y
Couch
Jill
J
Richardson
J Mark
JM
Cooper
Matthew J A
MJ
Wood
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000276:immunology; D051379:Mice; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051844:alpha-Synuclein / Q000276:immunology* / Q000378:metabolism
D017077:Culture Media, Conditioned; D016207:Cytokines; D051844:alpha-Synuclein