• The Korean Journal of Physiology and Pharmacology
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• v.15 no.2
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• pp.107-114
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• 2011

Neurofibrillary tangle (NFT) is a characteristic hallmark of Alzheimer's disease. GSK3β has been reported to play a major role in the NFT formation of tau. Dysfunction of autophagy might facilitate the aggregate formation of tau. The present study examined the role of GSK3${\beta}$-mediated phosphorylation of tau species on their autophagic degradation. We transfected wild type tau (T4), caspase-3-cleaved tau at Asp421 (T4C3), or pseudophosphorylated tau at Ser396/Ser404 (T4-2EC) in the presence of active or enzyme-inactive GSK3${\beta}$. Trehalose and 3-methyladenine (3-MA) were used to enhance or inhibit autophagic activity, respectively. All tau species showed increased accumulation with 3-MA treatment whereas reduced with trehalose, indicating that tau undergoes autophagic degradation. However, T4C3 and T4-2EC showed abundant formation of oligomers than T4. Active GSK3${\beta}$ in the presence of 3-MA resulted in significantly increased formation of insoluble tau aggregates. These results indicate that GSK3${\beta}$-mediated phosphorylation and compromised autophagic activity significantly contribute to tau aggregation.

• Bulletin of the Korean Chemical Society
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• v.33 no.11
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• pp.3671-3675
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• 2012

${\beta}$-Amyloid accumulation in the brain is a pathological hallmark of Alzheimer's disease (AD). Since early detection of ${\beta}$-amyloid may facilitate more successful and timely therapeutic interventions, many investigators have focused on developing AD diagnostic reagents that can penetrate the blood-brain barrier (BBB). Oleanolic acid (OA) is a substance found in a variety of plants that has been reported to prevent the progression of AD in mice. In this study, we synthesized and evaluated a new radioligand in which OA was conjugated to lactoferrin (Lf, an iron-binding glycoprotein that crosses the BBB) for the diagnosis of AD. In an in vitro study in which OA-Lf was incubated with ${\beta}$-amyloid (1-42) aggregates for 24 h, we found that OA-Lf effectively inhibited ${\beta}$-amyloid aggregation and fibril formation. In vivo studies demonstrated that $^{123}I$-OA-Lf brain uptake was higher than$^{123}I$-Lf uptake. Therefore, radiolabeled OA-Lf may have diagnostic potential for ${\beta}$-amyloid imaging.

• Molecules and Cells
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• v.38 no.2
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• pp.187-194
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• 2015

Thioredoxin (TRX) is a disulfide reductase present ubiquitously in all taxa and plays an important role as a regulator of cellular redox state. Recently, a redox-independent, chaperone function has also been reported for some thioredoxins. We previously identified nodulin-35, the subunit of soybean uricase, as an interacting target of a cytosolic soybean thioredoxin, GmTRX. Here we report the further characterization of the interaction, which turns out to be independent of the disulfide reductase function and results in the co-localization of GmTRX and nodulin-35 in peroxisomes, suggesting a possible function of GmTRX in peroxisomes. In addition, the chaperone function of GmTRX was demonstrated in in vitro molecular chaperone activity assays including the thermal denaturation assay and malate dehydrogenase aggregation assay. Our results demonstrate that the target of GmTRX is not only confined to the nodulin-35, but many other peroxisomal proteins, including catalase (AtCAT), transthyretin-like protein 1 (AtTTL1), and acyl-coenzyme A oxidase 4 (AtACX4), also interact with the GmTRX. Together with an increased uricase activity of nodulin-35 and reduced ROS accumulation observed in the presence of GmTRX in our results, especially under heat shock and oxidative stress conditions, it appears that GmTRX represents a novel thioredoxin that is co-localized to the peroxisomes, possibly providing functional integrity to peroxisomal proteins.

• Applied Chemistry for Engineering
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• v.32 no.1
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• pp.1-9
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• 2021

Alzheimer's disease (AD), an irreversible degenerative disorder, is associated with accumulation and aggregation of amyloid-β peptides, hyperphosphorylated tau proteins, and high level of metal ions in the brain. Up to date, there is no effective therapeutic agent to stop the progress of the disease and thus early and accurate diagnosis of AD has gained increasing attention in recent years. Among several diagnostic methods, an optical imaging using fluorescent probes is one of the most promising tools to visualize AD biomarkers. In this review, we will introduce fluorescent probes that can be applied to in vivo brain imaging of AD models and also their structure. It is expected that the present review will provide useful information to many scientists in the related research fields.

• BMB Reports
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• v.56 no.12
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• pp.657-662
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• 2023

Neurodegenerative diseases are characterized by distinct protein aggregates, such as those of α-synuclein and tau. Lysosomal defect is a key contributor to the accumulation and propagation of aberrant protein aggregates in these diseases. The discoveries of common proteinopathies in multiple forms of lysosomal storage diseases (LSDs) and the identification of some LSD genes as susceptible genes for those proteinopathies suggest causative links between LSDs and the proteinopathies. The present study hypothesized that defects in lysosomal genes will differentially affect the propagation of α-synuclein and tau proteins, thereby determining the progression of a specific proteinopathy. We established an imaging-based high-contents screening (HCS) system in Caenorhabditis elegans (C. elegans) model, by which the propagation of α-synuclein or tau is measured by fluorescence intensity. Using this system, we performed RNA interference (RNAi) screening to induce a wide range of lysosomal malfunction through knock down of 79 LSD genes, and to obtain the candidate genes with significant change in protein propagation. While some LSD genes commonly affected both α-synuclein and tau propagation, our study identified the distinct sets of LSD genes that differentially regulate the propagation of either α-synuclein or tau. The specificity and efficacy of these LSD genes were retained in the disease-related phenotypes, such as pharyngeal pumping behavior and life span. This study suggests that distinct lysosomal genes differentially regulate the propagation of α-synuclein and tau, and offer a steppingstone to understanding disease specificity.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.59-67
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• 2024

Background: Alzheimer's disease (AD) has memory impairment associated with aggregation of amyloid plaques and neurofibrillary tangles in the brain. Although anti-amyloid β (Aβ) protein antibody and chemical drugs can be prescribed in the clinic, they show adverse effects or low effectiveness. Therefore, the development of a new drug is necessarily needed. We focused on the cognitive function of Panax ginseng and tried to find active ingredient(s). We isolated panaxcerol D, a kind of glycosyl glyceride, from the non-saponin fraction of P. ginseng extract. Methods: We explored effects of acute or sub-chronic administration of panaxcerol D on cognitive function in scopolamine- or Aβ_25-35 peptide-treated mice measured by several behavioral tests. After behavioral tests, we tried to unveil the underlying mechanism of panaxcerol D on its cognitive function by Western blotting. Results: We found that pananxcerol D reversed short-term, long-term and object recognition memory impairments. The decreased extracellular signal-regulated kinases (ERK) or Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) in scopolamine-treated mice was normalized by acute administration of panaxcerol D. Glial fibrillary acidic protein (GFAP), caspase 3, NF-kB p65, synaptophysin and brainderived neurotrophic factor (BDNF) expression levels in Aβ_25-35 peptide-treated mice were modulated by sub-chronic administration of panaxcerol D. Conclusion: Pananxcerol D could improve memory impairments caused by cholinergic blockade or Aβ accumulation through increased phosphorylation level of ERK or its anti-inflammatory effect. Thus, panaxcerol D as one of non-saponin compounds could be used as an active ingredient of P. ginseng for improving cognitive function.

• Microbiology and Biotechnology Letters
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• v.29 no.4
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• pp.227-233
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• 2001

To maximize astaxanthin (3,3'-dihydroxy-$\beta\beta$'carotene-44'-dione) production by high density Haematococcus pluvialis cultures, various, media were examined Among tested media, \`Hong Kong Medium and Modified Bolds Basal Medium showed the best result for cell growth ( $2.0$\times$10^{ 6}$cells /mL) and for astaxanthin content per cell (9.7 mg astaxanthin mg/g cell), respectively, Maximum astasanthin concentration of 6.1mL was obtained at pH 7.5, $20^{\circ}C$~$25^{\circ}C$ Deficiencies of nitrogen source($NaNO_3$ and proteose-peptone) found to simulate astaxanthin formation Relatively low light inten- sity of $60\mu$E ($\m^2$s) was sutiable for vegetative cell growth while higher light intensity was required for higher astaxanthin accumulation.

• Macromolecular Research
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• v.13 no.3
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• pp.167-175
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• 2005

This review explores recent works involving the use of the self-assembled nanoparticles of bile acid-modified glycol chitosans (BGCs) as a new drug carrier for cancer therapy. BGC nanoparticles were produced by chemically grafting different bile acids through the use of l-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). The precise control of the size, structure, and hydrophobicity of the various BGC nanoparticles could be achieved by grafting different amounts of bile acids. The BGC nanoparticles so produced formed nanoparticles ranging in size from 210 to 850 nm in phosphate-buffered saline (PBS, pH=7.4), which exhibited substantially lower critical aggregation concentrations (0.038-0.260 mg/mL) than those of other low-molecular-weight surfactants, indicating that they possess high thermodynamic stability. The SOC nanoparticles could encapsulate small molecular peptides and hydrophobic anticancer drugs with a high loading efficiency and release them in a sustained manner. This review also highlights the biodistribution of the BGC nanoparticles, in order to demonstrate their accumulation in the tumor tissue, by utilizing the enhanced permeability and retention (EPR) effect. The different approaches used to optimize the delivery of drugs to treat cancer are also described in the last section.

• Korean Journal of Soil Science and Fertilizer
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• v.40 no.1
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• pp.4-11
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• 2007

There have been increasing concerns about decreasing crop productivity due to salt accumulation in greenhouse soils. The objective of the study was to investigate the impact of rice straw and woodchip application to a salt accumulated greenhouse soil on crop productivity and soil quality. The application of rice straw (RS) and woodchip (W) increased tomato yield and decreased blossom-end rot, and increased yield of Chinese cabbage compared with standard recommended fertilization ($204-103-122kg\;ha^{-1}\;N-P_2O_5-K_2O$ for tomato and $222-64-110kg\;ha^{-1}\;N-P_2O_5-K_2O$ for Chinese cabbage), while less soil residual nitrate, phosphatephosphorus, and potassium. In addition to the organic material application, fertilization reduction based on soil testing may also contribute to relatively low level of soil residual nutrients. Application of the organic material reduced soil bulk density presumably because of improved soil aggregation and structure, and increased biomass C and dehydrogenase activity. In comparison to rice straw, woodchip application resulted in higher crop yield, less amount of soil residual nitrate and lower soil EC, and greater biomass and dehydrogenase activity. The results obtained in this study indicateshowed that woodchip amendment along with reduced fertilization based on soil testing can be one of essential management practices for salt accumulated greenhouse soils.

• Childhood Kidney Diseases
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• v.2 no.2
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• pp.138-144
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• 1998

Purpose : The use of cyclosporine and mitomycin in various immunologic or neoplastic disorders has been known to cause wide-ranged nephrotoxic effects including thrombotic microangiopathy. However, the mechanism of nephrotoxicity of these drugs has not been studied adequately, so that present experimental study has been undertaken to find out whether these drugs can cause direct damage to the kidney and to clarify the pathogenetic mechanism of nephrotoxic effect of these drugs. Materials and methods : Sprague-Dawley rats weighing 250-300 gm were used for experimental animals and unilateral renal perfusion technique, modified from the method described by Hoyer et al was used. Isolation of left kidney from systemic circulation was made by clamping aorta and left renal vein and a hole was punctured in the anterior wall of the left renal vein. Cyclosporine (2.5 mg in 4 ml solution) and mitomycin (1.6 mg in 4ml solution) were infused through left renal artery and normal saline was used in control rats. Forty-eight hours after infusion of the drugs, animals were sacrificed and left kidney removed and processed for histologic examination. Total ischemic time of left kidney was less than 15 minutes: Results : Cyclosporine-perfused group showed severe swelling of glomerular endothelial ceil along with swelling of glomerular epithelial cell and interstitial vascular endothelial cell. Mitomycin-perfused group also showed severe swelling of glomerular endothelial and epithelial cells. And in addition to these findings, they demonstrated platelets aggregation, swelling and degranulation of platelets and fibrin accumulation in some of the capillaries, indicating occurrance of thrombotic microangiopathy. Conclusion : present experiment indicates that cyclosporine and mitomycin can cause direct toxic injury to renal endothelial cell. And this direct toxic damage to endothelial cell seems to be an important initiating event for the development of thrombotic microangiopathy.