scholarly journals Translocator Protein 18 kDa (TSPO) Deficiency Inhibits Microglial Activation and Impairs Mitochondrial Function

2020 ◽  
Vol 11 ◽  
Author(s):  
Rumeng Yao ◽  
Ruiyuan Pan ◽  
Chao Shang ◽  
Xiaoheng Li ◽  
Jinbo Cheng ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Microglial Activation ◽  
Translocator Protein ◽  
Translocator Protein 18 Kda

scholarly journals Effects of Translocator Protein (18 kDa) Ligands on Microglial Activation and Neuronal Death in the Quinolinic-Acid-Injected Rat Striatum

2012 ◽  
Vol 3 (2) ◽  
pp. 114-119 ◽  
Author(s):  
Katherine R. Leaver ◽  
Aaron Reynolds ◽  
Sylvie Bodard ◽  
Denis Guilloteau ◽  
Sylvie Chalon ◽  
...  
Keyword(s):  
Quinolinic Acid ◽  
Neuronal Death ◽  
Microglial Activation ◽  
Translocator Protein ◽  
Rat Striatum ◽  
Translocator Protein 18 Kda

scholarly journals Translocator Protein (18 kDa) Polymorphism (rs6971) Explains in-vivo Brain Binding Affinity of the PET Radioligand [18F]-FEPPA

2012 ◽  
Vol 32 (6) ◽  
pp. 968-972 ◽  
Author(s):  
Romina Mizrahi ◽  
Pablo M Rusjan ◽  
James Kennedy ◽  
Bruce Pollock ◽  
Benoit Mulsant ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Microglial Activation ◽  
Translocator Protein ◽  
Time Activity ◽  
Genetic Groups ◽  
Positron Emission ◽  
Translocator Protein 18 Kda ◽  
Human Brains ◽  
New Generation

[18F]-FEPPA binds to the 18-kDa translocator protein (TSPO) and is used in positron emission tomography (PET) to detect microglial activation. However, quantitative interpretations of the PET signal with new generation TSPO PET radioligands are confounded by large interindividual variability in binding affinity. This presents as a trimodal distribution, reflecting high-affinity binders (HABs), low-affinity binder (LAB), and mixed-affinity binders (MABs). Here, we show that one polymorphism (rs6971) located in exon 4 of the TSPO gene, which results in a nonconservative amino-acid substitution from alanine to threonine (Ala147Thr) in the TSPO protein, predicts [18F]-FEPPA total distribution volume in human brains. In addition, [18F]-FEPPA exhibits clearly different features in the shape of the time activity curves between genetic groups. Testing for the rs6971 polymorphism may allow quantitative interpretation of TSPO PET studies with new generation of TSPO PET radioligands.

scholarly journals TSPO Ligands PK11195 and Midazolam Reduce NLRP3 Inflammasome Activation and Proinflammatory Cytokine Release in BV-2 Cells

2020 ◽  
Vol 14 ◽  
Author(s):  
Hao Feng ◽  
Yongxin Liu ◽  
Rui Zhang ◽  
Yingxia Liang ◽  
Lina Sun ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Nlrp3 Inflammasome ◽  
Microglial Activation ◽  
Translocator Protein ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Bv2 Cells ◽  
Translocator Protein 18 Kda ◽  
Inflammatory Effect

Neuroinflammation related to microglial activation plays an important role in neurodegenerative diseases. Translocator protein 18 kDa (TSPO), a biomarker of reactive gliosis, its ligands can reduce neuroinflammation and can be used to treat neurodegenerative diseases. Therefore, we explored whether TSPO ligands exert an anti-inflammatory effect by affecting the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome, thereby inhibiting the release of inflammatory cytokines in microglial cells. In the present study, BV-2 cells were exposed to lipopolysaccharide (LPS) for 6 h to induce an inflammatory response. We found that the levels of reactive oxygen species (ROS), NLRP3 inflammasome, interleukin-1β (IL-1β), and interleukin-18 (IL-18) were significantly increased. However, pretreatment with TSPO ligands inhibited BV-2 microglial and NLRP3 inflammasome activation and significantly reduced the levels of ROS, IL-1β, and IL-18. Furthermore, a combination of LPS and ATP was used to activate the NLRP3 inflammasome. Both pretreatment and post-treatment with TSPO ligand can downregulate the activation of NLRP3 inflammasome and IL-1β expression. Finally, we found that TSPO was involved in the regulation of NLRP3 inflammasome with TSPO ligands treatment in TSPO knockdown BV2 cells. Collectively, these results indicate that TSPO ligands are promising targets to control microglial reactivity and neuroinflammatory diseases.

Structural and Functional Evolution of the Translocator Protein (18 kDa)

2012 ◽  
Vol 12 (4) ◽  
pp. 369-386 ◽  
Author(s):  
J. Fan ◽  
P. Lindemann ◽  
M. G.J. Feuilloley ◽  
V. Papadopoulos
Keyword(s):  
Translocator Protein ◽  
Functional Evolution ◽  
Translocator Protein 18 Kda
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