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Current status of PET-imaging probes of b-amyloid plaques
구재형,변영주 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.10
Alzheimer’s disease (AD) is the most commonform of dementia and is characterized by progressive cognitivedecline and memory loss. One of pathological hallmarks ofADis the accumulation and deposition of b-amyloid (Ab) plaqueswhich is a potential target for the early diagnosis of AD. Positron emission tomography (PET), a sensitive radionuclideimaging technique, has provided opportunities to detect Abplaques of AD. PET-imaging probes of Ab plaques have beenextensively developed during the last decade. [18F]Florbetapir,the 18F-labeled PET-imaging probe of Ab plaques, wasrecently approved by US Food and Drug Administration. Anumber of follow-on PET-imaging probes are currently beingdeveloped in academia and pharmaceutical companies. Thisarticle will discuss the recent development of PET-imagingprobes from [11C]PIB to [18F]Florbetapir, which are in clinictrials, and several follow-on probes in preclinical stage.
이나혜,사문선,홍유리,이창준,구재형 한국뇌신경과학회 2018 Experimental Neurobiology Vol.27 No.5
Medium-chain fatty acids (MCFAs) are mostly generated from dietary triglycerides and can penetrate the blood-brain barrier. Astrocytes in the brain use MCFAs as an alternative energy source. In addition, MCFAs have various regulatory and signaling functions in astrocytes. However, it is unclear how astrocytes sense and take up MCFAs. This study demonstrates that decanoic acid (DA; C10), a saturated MCFA and a ligand of Gαs protein-coupled receptors (Gαs-GPCRs), is a signaling molecule in energy metabolism in primary astrocytes. cAMP synthesis and lactate release were increased via a putative Gαs-GPCR and transmembrane adenylyl cyclase upon short-term treatment with DA. By contrast, monoamine oxidase B-dependent gamma-aminobutyric acid (GABA) synthesis was increased in primary cortical and hypothalamic astrocytes upon long-term treatment with DA. Thus, astrocytes respond to DA by synthesizing cAMP and releasing lactate upon short-term treatment, and by synthesizing and releasing GABA upon long-term treatment, similar to reactive astrocytes. Our data suggest that astrocytes in the brain play crucial roles in lipid-sensing via GPCRs and modulate neuronal metabolism or activity by releasing lactate via astrocyte-neuron lactate shuttle or GABA to influence neighboring neurons.
Hee Jin Cho,구재형 생화학분자생물학회 2021 BMB Reports Vol.54 No.12
Odorant receptors (ORs) account for about 60% of all humanG protein-coupled receptors (GPCRs). OR expression outsideof the nose has functions distinct from odor perception, andmay contribute to the pathogenesis of disorders including braindiseases and cancers. Glioma is the most common adult malignantbrain tumor and requires novel therapeutic strategies toimprove clinical outcomes. Here, we outlined the expressionof brain ORs and investigated OR expression levels in glioma. Although most ORs were not ubiquitously expressed in gliomas,a subset of ORs displayed glioma subtype-specific expression. Moreover, through systematic survival analysis on OR genes,OR51E1 (mouse Olfr558) was identified as a potential biomarkerof unfavorable overall survival, and OR2C1 (mouse Olfr15) wasidentified as a potential biomarker of favorable overall survivalin isocitrate dehydrogenase (IDH) wild-type glioma. In additionto transcriptomic analysis, mutational profiles revealed that somaticmutations in OR genes were detected in > 60% of gliomasamples. OR5D18 (mouse Olfr1155) was the most frequentlymutated OR gene, and OR5AR1 (mouse Olfr1019) showed IDHwild-type-specific mutation. Based on this systematic analysis andreview of the genomic and transcriptomic profiles of ORs inglioma, we suggest that ORs are potential biomarkers and therapeutictargets for glioma.