NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE26532 Query DataSets for GSE26532
Status Public on Feb 28, 2013
Title Neuron-released α-synuclein is an endogenous ligand of TLR2 for paracrine activation of microglia
Organism Rattus norvegicus
Experiment type Expression profiling by array
Summary Abnormal accumulation of aggregated proteins and sustained microglial activation are important contributors of neurodegenerative process in neurological diseases. Recent studies have shown that aggregation-prone proteins, such as a-synuclein, the protein implicated in Parkinson’s disease (PD), are released from neuronal cells and thus present in the extracellular fluid, pointing to the possible paracrine effects of these proteins on microglial immune responses. However, the mechanism underlying the disease-associated microglial activation and the role of neuronal proteins in this process remain unknown. Here, we show that extracellular a-synuclein released from neuronal cells is an endogenous ligand of toll-like receptor 2 (TLR2) and activates microglia, which in turn induces neurodegeneration. Interaction between neuron-released a-synuclein and TLR2 and subsequent activation of the TLR2 signaling were demonstrated comprehensively by using computational modeling of signaling network and by the experimental validation in TLR2-deficient microglia both in vitro and in vivo. In contrast to the neuron-released a-synuclein, recombinant a-synuclein proteins, including monomer, oligomer, fibril, or nitrated forms, were not able to interact or activate TLR2, suggesting that neuronal cells have a mechanism of enriching specific forms of a-synuclein capable of activating TLR2 during the process of releasing this protein. Taken together, the results suggest that both neuron-released extracellular a-synuclein and TLR2 might be novel therapeutic targets for modifying neuroinflammation in PD and related neurodegenerative diseases.
 
Overall design We collected culture media from differentiated SH-SY5Y cells overexpressing either human a-synuclein (alpha-SCM) or beta-galactosidase (LZCM) and treat these media to primary rat microglia at the concentration of a-synuclein of 1.1M. Transcriptome analyses with microglial cells treated with either aSCM or LZCM at two different time points, 6 h and 24 h.
 
Contributor(s) Lee S, Hwang D
Citation(s) 23463005, 24743837
Submission date Jan 10, 2011
Last update date Jul 29, 2014
Contact name Sungyong You
E-mail(s) Sungyong.You@cshs.org
Organization name Cedars-Sinai Medical Center
Department Surgery
Lab Freeman Lab.
Street address Beverly Blvd 8400
City LA
State/province CA
ZIP/Postal code 90048
Country USA
 
Platforms (1)
GPL6101 Illumina ratRef-12 v1.0 expression beadchip
Samples (12)
GSM652298 6hr LacZ 1
GSM652299 6hr LacZ 2
GSM652300 6hr LacZ 3
Relations
BioProject PRJNA136651

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE26532_RAW.tar 2.8 Mb (http)(custom) TAR
GSE26532_non-normalized.txt.gz 1.6 Mb (ftp)(http) TXT
Processed data included within Sample table

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap