• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.2
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• pp.69-72
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• 2016

Since the translocator protein (TSPO) is involved in neurodegeneration diseases, many scientists' interest has been focused on the development of a ligand targeting TSPO. A novel compound based on pyrazolo[1,5 -a] pyrimidine structure, DPA-714, has been studied and considered as a TSPO ligand with high affinity. In this highlight review, several researches for the novel radioligand for the translocator protein are illustrated.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.2
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• pp.95-97
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• 2015

The translocator protein (TSPO) is one of the important targets for Positron Emission Tomography (PET) imaging because it is associated with brain cancer, stroke, and neurodegeneration. Recently, a novel quinoline compound with high affinity agent for the translocator protein has been developed. In this highlight review, major studies for the quinoline compound are described.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.1
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• pp.37-42
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• 2016

The translocator protein (TSPO) has attracted scientist's attention for Positron Emission Tomography (PET) imaging due to correlation with brain cancer, stroke, and neurodegeneration. Recently, GE-180, a novel tricyclic derivative has been developed as a new high affinity agent for the TSPO and evaluated to confirm a possibility for the TSPO ligand. In this highlight review, several studies for the novel TSPO radiotracer are described.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.1
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• pp.33-37
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• 2022

Translocator protein (TSPO) is associated with neurodegeneration diseases, and the development of potent ligands with high affinity to TSPO was valuable study for many scientists. Specially, pyrazolo[1,5-a]pyrimidine moiety has been employed for development of new TSPO ligands with good properties. In this highlight review, the development of [¹⁸F]F-DPA as a promising TSPO ligand as PET tracer is described.

• Biomolecules & Therapeutics
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• v.14 no.3
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• pp.132-136
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• 2006

Aryl hydrocarbon receptor nuclear translocator (Arnt) belongs to bHLH-PAS protein family. Here, we study the role of Arnt in both cell growth and glucose metabolism. Our results demonstrated that the absence of Arnt does affect ATP homeostasis but not cell growth in monolayer-cultured mouse hepatoma cells. ATP level of Arnt defective BpRc1 hepatoma cells is less than that of wild type hepatoma cells in both normoxia and hypoxia. BpRc1 cells also fail to increase the expression of glycolytic enzymes in response to hypoxia. Our results suggest that Arnt is essential for glucose metabolism and ATP production but not for cell growth.

• BMB Reports
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• v.53 no.1
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• pp.20-27
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• 2020

Translocator protein (TSPO), also known as peripheral benzodiazepine receptor, is a transmembrane protein located on the outer mitochondria membrane (OMM) and mainly expressed in glial cells in the brain. Because of the close correlation of its expression level with neuropathology and therapeutic efficacies of several TSPO binding ligands under many neurological conditions, TSPO has been regarded as both biomarker and therapeutic target, and the biological functions of TSPO have been a major research focus. However, recent genetic studies with animal and cellular models revealed unexpected results contrary to the anticipated biological importance of TSPO and cast doubt on the action modes of the TSPO-binding drugs. In this review, we summarize recent controversial findings on the discrepancy between pharmacological and genetic studies of TSPO and suggest some future direction to understand this old and mysterious protein.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.1
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• pp.56-65
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• 2021

TSPO, an 18-kDa translocator protein, is a peripheral-type benzodiazepine receptor that has been associated to a variety of biological activities such as apoptosis, steroidogenesis, and cell proliferation. Because TSPO overexpression has been found in various forms of cancer, it has recently become one of the most appealing biological targets for cancer therapies and detection. In order to create new optical imaging agents for improved diagnostics, we synthesized a novel dimeric fluorescent TSPO ligand based on PRB28 structure and SCy5.5. Following the preparation of the novel TSPO ligand, in vivo and ex vivo imaging tests were performed to examine the tumor uptake characteristics of the fluorescent TSPO ligand in a glioma animal model, and it was found that novel TSPO ligand was accumulated in glioma. These results suggested that novel dimeric fluorescent TSPO ligand will be applied to detect glioma.

• Journal of Life Science
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• v.12 no.5
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• pp.555-560
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• 2002

The molecular composition of the postsynaptic density (PSD) is largely hon. In this report, an electroelution protocol was demonstrated to be used for efficient isolation of PSD proteins with diverse molecular sizes. Using this protocol, a 31 kDa protein in the 1% n-octyl glucoside-insoluble PSD fraction (termed as PSD31) was purified from SDS-gels, and internal peptides were determined for amino acid sequences. The amino acid sequences of the PSD31 were highly homologous with the adenine nucleotide translocator 1 (ANTI). The association of ANTl with PSD suggests presence of a mechanism in synapses for releasing adenosine nucleotides into the extracellular space.

• Molecules and Cells
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• v.43 no.11
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• pp.935-944
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• 2020

Aryl hydrocarbon receptor nuclear translocator (ARNT) plays an essential role in maintaining cellular homeostasis in response to environmental stress. Under conditions of hypoxia or xenobiotic exposure, ARNT regulates the subset of genes involved in adaptive responses, by forming heterodimers with hypoxia-inducible transcription factors (HIF1α and HIF2α) or aryl hydrocarbon receptor (AhR). Here, we have shown that ARNT interacts with DDB1 and CUL4-associated factor 15 (DCAF15), and the aryl sulfonamides, indisulam and E7820, induce its proteasomal degradation through Cullin-RING finger ligase 4 containing DCAF15 (CRL4^DCAF15) E3 ligase. Moreover, the two known neo-substrates of aryl sulfonamide, RNA-binding motif protein 39 (RBM39) and RNA-binding motif protein 23 (RBM23), are not required for ARNT degradation. In line with this finding, aryl sulfonamides inhibited the transcriptional activities of HIFs and AhR associated with ARNT. Our results collectively support novel regulatory roles of aryl sulfonamides in both hypoxic and xenobiotic responses.

• Dementia and Neurocognitive Disorders
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• v.21 no.2
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• pp.71-78
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• 2022

Background and Purpose: The expression of the 18-kDA mitochondrial translocator protein (TSPO) in the brain is an attractive target to study neuroinflammation. However, the binding properties of TSPO ligands are reportedly dependent on genetic polymorphism of the TSPO gene (rs6971). The objective of this study is to investigate the rs6971 gene polymorphism in the Korean population. Methods: We performed genetic testing on 109 subjects including patients with mild cognitive impairment, Alzheimer's disease (AD) dementia, non-AD dementia, and cognitively unimpaired participants. Magnetic resonance imaging scans and detailed neuropsychological tests were also performed, and 29 participants underwent ¹⁸F-DPA714 PET scans. Exon 4 of the TSPO gene containing the polymorphism rs6971 (Ala or Thr at position 147) was polymerase chain reaction amplified and sequenced using the Sanger method. The identified rs6971 genotype codes (C/C, C/T, or T/T) of the TSPO protein generated high-, mixed-, or low-affinity binding phenotypes (HABs, MABs, and LABs), respectively. Results: We found that 96.3% of the study subjects were HAB (105 out of 109 subjects), and 3.7% of the subjects were MAB (4 out of 109 subjects). ¹⁸F-DPA-714 PET scans showed nonspecific binding to the thalamus and brainstem, and increased tracer uptake throughout the cortex in cognitively impaired patients. The participant with the MAB polymorphism had a higher DPA714 signal throughout the cortex. Conclusions: The majority of Koreans are HAB (aprox. 96%). Therefore, the polymorphism of the rs6971 gene would have a smaller impact on the availability of second-generation TSPO PET tracers.