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Published on: January 7, 2014
Translocator protein (18 kDa) regulates the microglial phenotype in Parkinson's disease through P47
Xue Xue1, Rui Duan2, Guoyan Zheng1
1Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Abstract:
Numerous studies have suggested that the phenotypic transformation of microglia plays a role in the pathogenesis of Parkinson's disease (PD). Translocator protein (TSPO) is an 18 kDa translocator membrane protein that acts as a marker of neuroinflammation and suppresses neuroinflammation; however, its underlying mechanism remains unclear. Although TSPO ligands were found to be protective in several neurodegenerative paradigms, few studies have evaluated their effects on microglial polarization, and underlying mechanisms need to be explored. In the present study, we examined the effects of TSPO and PK11195, a TSPO ligand, on lipopolysaccharide (LPS)+interferon (IFN)-γ-induced inflammatory factors and oxidative stress in microglia using enzyme-linked immunosorbent assay. The effect of TSPO and PK11195 on LPS+IFN-γ-induced microglial cell apoptosis was examined using immunofluorescence (IF), flow cytometry, and western blotting. The interaction between TSPO and P47 was investigated using IF and co-immunoprecipitation analysis. In vivo experiments confirmed the influence of TSPO and its ligand on motility, a-Syn, and dopaminergic neuronal damage. Our findings indicate that TSPO may regulate the microglial phenotype in PD via P47, suggesting a potential role in anti-PD therapy.
Insights
Translocator protein (TSPO) and its ligand PK11195 influence microglial activation in Parkinson's disease (PD) models. TSPO may regulate microglial phenotype via P47, offering a potential therapeutic target for PD.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglial activation is implicated in Parkinson's disease (PD) pathogenesis.
- Translocator protein (TSPO) is a marker of neuroinflammation with unclear mechanisms.
- TSPO ligands show protective effects in neurodegeneration, but their impact on microglial polarization needs investigation.
Purpose of the Study:
- To investigate the effects of TSPO and its ligand PK11195 on microglial inflammatory responses and apoptosis.
- To explore the underlying mechanisms of TSPO's role in microglial activation in PD.
- To assess the in vivo effects of TSPO and its ligand on PD-related pathology.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) for inflammatory factors and oxidative stress.
- Immunofluorescence (IF), flow cytometry, and western blotting for apoptosis assessment.
- Co-immunoprecipitation and IF for TSPO-P47 interaction analysis; in vivo studies.
Main Results:
- TSPO and PK11195 modulated lipopolysaccharide (LPS)+interferon (IFN)-γ-induced inflammatory factors and oxidative stress in microglia.
- TSPO and PK11195 affected LPS+IFN-γ-induced microglial apoptosis.
- TSPO-P47 interaction was confirmed; in vivo experiments showed TSPO's influence on motility, alpha-synuclein (a-Syn), and dopaminergic neuronal damage.
Conclusions:
- TSPO plays a role in regulating microglial phenotype in Parkinson's disease, potentially through interaction with P47.
- TSPO and its ligand PK11195 demonstrate potential as therapeutic targets for Parkinson's disease.
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