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https://www.readbyqxmd.com/read/28901441/profiling-of-differentially-expressed-genes-in-adipose-tissues-of-multiple-symmetric-lipomatosis
#1
Ke Chen, Linghao Wang, Wenjun Yang, Changfa Wang, Gui Hu, Zhaohui Mo
Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by aberrant multiple and symmetric subcutaneous adipose tissue accumulation in the face, neck, shoulders, back, chest and abdomen, severely affecting the quality of life of patients. At present, precise MSL etiology and pathogenesis remain to be elucidated. The present study first utilized a digital gene expression technique with a next‑generation sequencing platform to profile differentially expressed genes in three cases of MSL vs. normal control tissue...
September 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900831/-18-f-dpa-714-pet-imaging-reveals-global-neuroinflammation-in-zika-virus-infected-mice
#2
Kyle Kuszpit, Bradley S Hollidge, Xiankun Zeng, Robert G Stafford, Sharon Daye, Xiang Zhang, Falguni Basuli, Joseph W Golden, Rolf E Swenson, Darci R Smith, Thomas M Bocan
PURPOSE: The association of Zika virus (ZIKV) infection and development of neurological sequelae require a better understanding of the pathogenic mechanisms causing severe disease. The purpose of this study was to evaluate the ability and sensitivity of positron emission tomography (PET) imaging using [(18)F]DPA-714, a translocator protein (TSPO) 18 kDa radioligand, to detect and quantify neuroinflammation in ZIKV-infected mice. PROCEDURES: We assessed ZIKV-induced pathogenesis in wild-type C57BL/6 mice administered an antibody to inhibit type I interferon (IFN) signaling...
September 12, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28899788/the-translocator-protein-ligand-xbd173-improves-clinical-symptoms-and-neuropathological-markers-in-the-sjl-j-mouse-model-of-multiple-sclerosis
#3
Géraldine Leva, Christian Klein, Jérémie Benyounes, François Hallé, Frédéric Bihel, Nicolas Collongues, Jérôme De Seze, Ayikoe-Guy Mensah-Nyagan, Christine Patte-Mensah
Multiple sclerosis (MS) is a severe autoimmune disease characterized by inflammatory, demyelinating and neurodegenerative components causing motor, sensory, visual and/or cognitive symptoms. The relapsing-remitting MS affecting 85% of patients is reliably mimicked by the proteolipid-protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE) SJL/J-mouse model. Significant progress was made for MS treatment but the development of effective therapies devoid of severe side-effects remains a great challenge...
September 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28893493/brain-tspo-imaging-and-gray-matter-volume-in-schizophrenia-patients-and-in-people-at-ultra-high-risk-of-psychosis-an-11-c-pbr28-study
#4
Sudhakar Selvaraj, Peter S Bloomfield, Bo Cao, Mattia Veronese, Federico Turkheimer, Oliver D Howes
Patients with schizophrenia show whole brain and cortical gray matter (GM) volume reductions which are progressive early in their illness. Microglia, the resident immune cells in the CNS, phagocytose neurons and synapses. Some post mortem and in vivo studies in schizophrenia show evidence for elevated microglial activation compared to matched controls. However, it is currently unclear how these results relate to changes in cortical structure. METHODS: Fourteen patients with schizophrenia and 14 ultra high risk for psychosis (UHR) subjects alongside two groups of age and genotype matched healthy controls received [(11)C]PBR28 PET scans to index TSPO expression, a marker of microglial activation and a 3T MRI scan...
September 8, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28875261/the-low-affinity-binding-of-second-generation-radiotracers-targeting-tspo-is-associated-with-a-unique-allosteric-binding-site
#5
Camilo Rojas, Marigo Stathis, Jennifer M Coughlin, Martin Pomper, Barbara S Slusher
[(11)C]-PK11195 (PK11195) has been widely used with positron emission tomography (PET) to assess levels of the translocator protein 18 kDa (TSPO) as a marker of neuroinflammation. Recent ligands, such as [(11)C]-PBR28 and [(11)C]-DPA713, have improved signal-to-noise ratio and specificity for TSPO over PK11195. However, these second generation radiotracers exhibit binding differences due to a single polymorphism (rs6971) that leads to three genotypes: C/C, C/T and T/T associated with high, mixed and low binding affinities, respectively...
September 5, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28858490/exploiting-the-4-phenylquinazoline-scaffold-for-the-development-of-high-affinity-fluorescent-probes-for-the-translocator-protein-tspo
#6
Ciro Milite, Elisabetta Barresi, Eleonora Da Pozzo, Barbara Costa, Monica Viviano, Amalia Porta, Anna Messere, Gianluca Sbardella, Federico Da Settimo, Ettore Novellino, Sandro Cosconati, Sabrina Castellano, Sabrina Taliani, Claudia Martini
The quinazoline class was exploited to search for a new translocator protein (TSPO) fluorescent probe endowed with improved affinity and residence time (RT). Computational studies on an "in-house" collection of quinazoline derivatives, featuring highly steric demanding groups at the amide nitrogen, suggested that, despite their molecular extension, these ligands are still easily lodged in the TSPO binding site. Binding assays supported this hypothesis, highlighting a low nanomolar/subnanomolar affinity of these ligands, together with a higher RT of the representative compound 11 with respect to our previously reported indole-based fluorescent probe...
September 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28844784/dieldrin-induced-neurotoxicity-involves-impaired-mitochondrial-bioenergetics-and-an-endoplasmic-reticulum-stress-response-in-rat-dopaminergic-cells
#7
Jordan T Schmidt, Anna Rushin, Jonna Boyda, Christopher Laurence Souders, Christopher J Martyniuk
Mitochondria are sensitive targets of environmental chemicals. Dieldrin (DLD) is an organochlorine pesticide that remains a human health concern due to high lipid bioaccumulation, and it has been epidemiologically associated to an increased risk for Parkinson's disease (PD). As mitochondrial dysfunction is involved in the etiology of PD, this study aimed to determine whether DLD impaired mitochondrial bioenergetics in dopaminergic cells. Rat immortalized dopaminergic N27 cells were treated for 24 or 48h with one dose of either a solvent control, 2...
August 24, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28822038/translocator-protein-pet-imaging-in-a-preclinical-prostate-cancer-model
#8
Mohammed N Tantawy, H Charles Manning, Todd E Peterson, Daniel C Colvin, John C Gore, Wenfu Lu, Zhenbang Chen, C Chad Quarles
PURPOSE: The identification and targeting of biomarkers specific to prostate cancer (PCa) could improve its detection. Given the high expression of translocator protein (TSPO) in PCa, we investigated the use of [(18)F]VUIIS1008 (a novel TSPO-targeting radioligand) coupled with positron emission tomography (PET) to identify PCa in mice and to characterize their TSPO uptake. PROCEDURES: Pten(pc-/-), Trp53(pc-/-) prostate cancer-bearing mice (n = 9, 4-6 months old) were imaged in a 7T MRI scanner for lesion localization...
August 18, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28821920/tspo-pet-for-glioma-imaging-using-the-novel-ligand-18-f-ge-180-first-results-in-patients-with-glioblastoma
#9
Nathalie L Albert, M Unterrainer, D F Fleischmann, S Lindner, F Vettermann, A Brunegraf, L Vomacka, M Brendel, V Wenter, C Wetzel, R Rupprecht, J-C Tonn, C Belka, P Bartenstein, M Niyazi
OBJECTIVE: The 18-kDa mitochondrial translocator protein (TSPO) was reported to be upregulated in gliomas. (18)F-GE-180 is a novel 3rd generation TSPO receptor ligand with improved target-to-background contrast compared to previous tracers. In this pilot study, we compared PET imaging with (18)F-GE-180 and MRI of patients with untreated and recurrent pretreated glioblastoma. METHODS: Eleven patients with histologically confirmed IDH wildtype gliomas (10 glioblastomas, 1 anaplastic astrocytoma) underwent (18)F-GE-180 PET at initial diagnosis or recurrence...
August 19, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28820402/does-signaling-of-estrogen-related-receptors-affect-structure-and-function-of-bank-vole-leydig-cells
#10
P Pawlicki, A Milon, M Zarzycka, J Galas, W Tworzydlo, A Kaminska, L Pardyak, K Lesniak, A Pacwa, B Bilinska, E Gorowska-Wojtowicz, M Kotula-Balak
To get a deeper insight into the function of estrogen-related receptors (ERRs) and dissect underlying mechanism in Leydig cells, ERRs (type α, β and γ) were blocked or activated in testes of adult bank voles (Myodes glareolus) which show seasonal changes in the intratesticular sex hormones level. Both actively reproducing animals (long day conditions; LD) and those with regression of the reproductive system (short day conditions; SD) received intraperitoneal injections of selective ERRα antagonist 3-[4-(2,4-Bis-trifluoromethylbenzyloxy)-3-methoxyphenyl]-2-cyano-N-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)acrylamide (XCT 790) or selective ERRβ/ERRγ agonist N-(4-(Diethylaminobenzylidenyl)-N'-(4-hydroxybenzoyl)-hydrazine (DY131) (50 μ/kg bw; six doses every other day)...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28818984/pseudo-reference-regions-for-glial-imaging-with-11-c-pbr28-investigation-in-two-clinical-cohorts
#11
Daniel Strakis Albrecht, Marc David Normandin, Sergey Shcherbinin, Dustin W Wooten, Adam J Schwarz, Nicole R Zurcher, Vanessa N Barth, Nicolas J Guehl, Oluwaseun Johnson-Akeju, Nazem Atassi, Mattia Veronese, Federico Turkheimer, Jacob M Hooker, Marco Luciano Loggia
The translocator protein (TSPO) is a commonly used imaging target to investigate neuroinflammation. While TSPO imaging demonstrates great promise, its signal exhibits substantial interindividual variability, which needs to be accounted for to uncover group effects that are truly reflective of neuroimmune activation. Recent evidence suggests that relative metrics computed using pseudo-reference approaches can minimize within-group variability, and increase sensitivity to detect physiologically meaningful group differences...
August 17, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28811616/synthesis-free-pet-imaging-of-brown-adipose-tissue-and-tspo-via-combination-of-disulfiram-and-64-cucl2
#12
Jing Yang, Jian Yang, Lu Wang, Anna Moore, Steven H Liang, Chongzhao Ran
PET imaging is a widely applicable but a very expensive technology. On-site synthesis is one important contributor to the high cost. In this report, we demonstrated the feasibility of a synthesis-free method for PET imaging of brown adipose tissue (BAT) and translocator protein 18 kDa (TSPO) via a combination of disulfiram, an FDA approved drug for alcoholism, and (64)CuCl2 (termed (64)Cu-Dis). In this method, a step-wise injection protocol of (64)CuCl2 and disulfiram was used to accomplish the purpose of synthesis-free...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28775204/impact-of-endothelial-tspo-on-the-quantification-of-18-f-dpa-714
#13
Catriona Wimberley, Sonia Lavisse, Vincent Brulon, Marie-Anne Peyronneau, Claire Leroy, Benedetta Bodini, Philippe Remy, Bruno Stankoff, Irene Buvat, Michel Bottlaender
(18)F-DPA-714 is a second generation tracer for positron emission tomography (PET) imaging of the 18 kDa translocator protein (TSPO), a marker of neuroinflammation. Analysis and interpretation of TSPO PET are challenging especially due to a basal expression of TSPO. The aim of this study was to evaluate a compartmental model which accounts for endothelial TSPO binding on PET scans from a cohort of healthy subjects. Methods: Fifteen healthy subjects (9 high-affinity binders and 6 mixed-affinity binders) underwent (18)F-DPA-714 PET scans with arterial blood sampling and metabolite analysis...
August 3, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28771957/bridging-pharmaceutical-chemistry-with-drug-and-nanoparticle-targeting-to-investigate-the-role-of-the-18-kda-translocator-protein-tspo
#14
REVIEW
Rosa Maria Iacobazzi, Antonio Lopalco, Annalisa Cutrignelli, Valentino Laquintana, Angela Lopedota, Massimo Franco, Nunzio Denora
An interesting mitochondrial biomarker is the 18-kDa mitochondrial translocator protein (TSPO). Decades of study have shown that this protein plays an important role in a wide range of cellular functions, including opening of the mitochondrial permeability transition pore as well as programmed cell death and proliferation. Variations in TSPO expression have been correlated to different diseases, from tumors to endocrine and neurological disorders. TSPO has therefore become an appealing target for both early diagnosis and selective mitochondrial drug delivery...
August 3, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28755381/molecular-modeling-of-transporters-from-low-resolution-cryo-electron-microscopy-map-to-conformational-exploration-the-example-of-tspo
#15
Aurore Vaitinadapoule, Catherine Etchebest
This chapter describes a protocol to establish a three-dimensional (3D) model of a protein and to explore its conformational landscape. It combines predictions from up-to-date bioinformatics methods with low-resolution experimental data. It also proposes to examine rapidly the dynamics of the protein using molecular dynamics simulations with a coarse-grained force field. Tools for analyzing these trajectories are suggested as well as those for constructing all-atoms models. Thus, starting from a protein sequence and using free software, the user can get important conformational information, which might improve the knowledge about the protein function...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28755378/solid-state-nmr-of-membrane-protein-reconstituted-in-proteoliposomes-the-case-of-tspo
#16
Lucile Senicourt, Luminita Duma, Vassilios Papadopoulos, Jean-Jacques Lacapere
Structural studies of membrane proteins (MP) in a native or native-like environment remain a challenge. X-ray crystallography of three-dimensional crystals of MP in lipids and cryo-electron microscopy of two-dimensional crystals also in lipids have given atomic structures of several MP. Recent developments of solid-state NMR (ssNMR) provided structural data of MP in lipids and should give access to the dynamic behavior of MP's in a native-like environment. Preparation of samples for ssNMR is not trivial with overexpressed proteins since purified recombinant MP have to be reincorporated in proteoliposomes and concentrated in the small volume of the rotor used for ssNMR studies...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28755361/recombinant-overexpression-of-mammalian-tspo-isoforms-1-and-2
#17
Lucile Senicourt, Soria Iatmanen-Harbi, Claude Hattab, Mariano Anibal Ostuni, Marie-France Giraud, Jean-Jacques Lacapere
TSPO is a 18 kDa membrane protein that exists in mammalian as two isoforms 1 and 2. They are involved in different functions and are located in different membranes. TSPO1 is mainly located in outer mitochondrial membrane, whereas TSPO2 is encountered in plasma membrane of red blood cells. Determination of their structures is a milestone to understand their function. Their natural abundance is not sufficient to get large amounts usually required for structural studies. We described heterologous overexpression in both bacterial and cell-free system and purification on immobilized-metal affinity chromatography (IMAC) of both proteins...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28754131/a-translocator-protein-18%C3%A2-kda-agonist-protects-against-cerebral-ischemia-reperfusion-injury
#18
Han-Dong Li, Minshu Li, Elaine Shi, Wei-Na Jin, Kristofer Wood, Rayna Gonzales, Qiang Liu
BACKGROUND: Cerebral ischemia is a leading cause of death and disability with limited treatment options. Although inflammatory and immune responses participate in ischemic brain injury, the molecular regulators of neuroinflammation after ischemia remain to be defined. Translocator protein 18 kDa (TSPO) mainly localized to the mitochondrial outer membrane is predominantly expressed in glia within the central nervous system during inflammatory conditions. This study investigated the effect of a TSPO agonist, etifoxine, on neuroinflammation and brain injury after ischemia/reperfusion...
July 28, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28741281/microglial-depletion-and-activation-a-11-c-pbr28-pet-study-in-nonhuman-primates
#19
Ansel T Hillmer, Daniel Holden, Krista Fowles, Nabeel Nabulsi, Brian L West, Richard E Carson, Kelly P Cosgrove
BACKGROUND: The 18-kDa translocator protein (TSPO) is an important target for assessing neuroimmune function in brain with positron-emission tomography (PET) imaging. The goal of this work was to assess two [(11)C]PBR28 imaging paradigms for measuring dynamic microglia changes in Macaca mulatta. METHODS: Dynamic [(11)C]PBR28 PET imaging data with arterial blood sampling were acquired to quantify TSPO levels as [(11)C]PBR28 V T. Scans were acquired at three timepoints: baseline, immediately post-drug, and prolonged post-drug...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28738332/neuroprogression-and-immune-activation-in-major-depressive-disorder
#20
Jeffrey H Meyer
Traditionally, the neurobiology of major depressive disorder (MDD) has been largely considered from the perspective of the state of major depressive episodes (MDE) versus being in remission, but the current accumulation of disease markers, largely acquired cross-sectionally, is strongly suggestive of neuroprogressive aspects of MDD. This chapter focuses on the changes in disease markers involved in the reorganization of the nervous system in MDD, including the translocator protein (TSPO; an index of microglial activation), glial fibrillary acidic protein (GFAP; an index of astroglial activation), [11C]harmine (a marker of monoamine oxidase A; MAO-A), and several other indices (metabotropic glutamate receptor 5 [mGluR5], excitatory amino acid transporters, and magnetic resonance imaging spectroscopy measurements) of glutamate dysregulation...
2017: Modern Trends in Pharmacopsychiatry
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