• Journal of Microbiology and Biotechnology
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• 제13권5호
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• pp.809-814
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• 2003

${\beta}-amyloid$ ($A{\beta}$) peptides from the proteolytic processing of ${\beta}-amyloid$ precursor protein (${\beta}-APP$) aggregates in the brain to form senile plaques, and their aggregation plays a key role in pathogenesis of Alzheimer's disease (AD). To isolate an active compound that has an $A{\beta}$ aggregation-inhibitory activity, 2,000 microbial metabolite libraries were screened based on their ability to inhibit $A{\beta}$ aggregation by using both Congo red and thioflavin T assays. As a result, a water-soluble fraction of a soil microorganism, KK565, showed a potent $A{\beta}$ aggregation-inhibitory activity. The strain was identified as Streptomyces species, based on the cultural and morphological characteristics, the presence of diaminopimelic acid in the cell wall, and the sugar patterns for the whole-cell extract. In addition, the purification of active principle resulted in identifying a heat-unstable protein responsible for the $A{\beta}$ aggregation-inhibitory activity.

• Molecules and Cells
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• 제24권1호
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• pp.113-118
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• 2007

The brains of Alzheimer's disease (AD) patients are characterized by large deposits of amyloid beta peptide ($A{\beta}$). $A{\beta}$ is known to increase free radical production in nerve cells, leading to cell death that is characterized by lipid peroxidation, free radical formation, protein oxidation, and DNA/RNA oxidation. In this study, we selected an extract of Gardenia jasminoides by screening, and investigated its ameliorating effects on $A{\beta}$-induced oxidative stress using PC12 cells. The effects of the extract were evaluated using the 2',7'-dichlorofluorescein diacetate (DCF-DA) assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. To find the active component, the ethanol extract was partitioned with hexane, chloroform, and ethyl acetate, respectively, and the active component was purified by silica-gel column chromatography and HPLC. The results suggested that Gardenia jasminoides extract can reduce the cytotoxicity of $A{\beta}$ in PC 12 cells, possibly by reducing oxidative stress.

• 대한의생명과학회지
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• 제24권4호
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• pp.418-425
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• 2018

Amyloid brain positron emission tomography (PET) images are visually and subjectively analyzed by the physician with a lot of time and effort to determine the ${\beta}$-Amyloid ($A{\beta}$) deposition. We designed a convolutional neural network (CNN) model that predicts the $A{\beta}$-positive and $A{\beta}$-negative status. We performed 18F-florbetaben (FBB) brain PET on controls and patients (n=176) with mild cognitive impairment and Alzheimer's Disease (AD). We classified brain PET images visually as per the on the brain amyloid plaque load score. We designed the visual geometry group (VGG16) model for the visual assessment of slice-based samples. To evaluate only the gray matter and not the white matter, gray matter masking (GMM) was applied to the slice-based standard samples. All the performance metrics were higher with GMM than without GMM (accuracy 92.39 vs. 89.60, sensitivity 87.93 vs. 85.76, and specificity 98.94 vs. 95.32). For the patient-based standard, all the performance metrics were almost the same (accuracy 89.78 vs. 89.21), lower (sensitivity 93.97 vs. 99.14), and higher (specificity 81.67 vs. 70.00). The area under curve with the VGG16 model that observed the gray matter region only was slightly higher than the model that observed the whole brain for both slice-based and patient-based decision processes. Amyloid brain PET images can be appropriately analyzed using the CNN model for predicting the $A{\beta}$-positive and $A{\beta}$-negative status.

• 동의신경정신과학회지
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• 제19권2호
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• pp.151-163
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• 2008

Objective : Recent studies indicate that the deposition of beta-amyloid ($A{\beta}$) is related in the pathogenesis of Alzheimer's disease (AD), but the underlying mechanism is still not clear. Method : To investigate the potential cellular functions of APP and LMK02, we use transgenic drosophila as a model was treated with either LMK02, and the effect in APP expression was determined by climbing assay. LMK02 have been shown to be neuroprotective in fly model systems. We asked whether dietary supplementation with LMK02 would influence behavior and AD-like pathology in a transgenic fly model. Result LMK02 water extract have attenuated fly death in vivo. LMK02-treated fly increased percentage of flight ability more longly and survival ratio more than controls. APP-GRIM drosophila treated with LMK02 had significantly less accumulation of APP deposition in the eye and brain as compared to control drosophila. Conclusion : These results suggest that LMK02 prevent APP-induced neurotoxicity through attenuating flies death induced by APP, and may be useful as potential therapeutic agents for AD.

• Journal of Microbiology and Biotechnology
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• 제31권6호
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• pp.867-874
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• 2021

Epalrestat (EPS) is a brain penetrant aldose reductase inhibitor, an approved drug currently used for the treatment of diabetic neuropathy. At near-plasma concentration, EPS induces glutathione biosynthesis, which in turn reduces oxidative stress in the neuronal cells. In this study, we found that EPS reduces neurodegeneration by inhibiting reactive oxygen species (ROS)-induced oxidative injury, mitochondrial membrane damage, apoptosis and tauopathy. EPS treatment up to 50 µM did not show any toxic effect on SH-SY5Y cell line (neuroblastoma cells). However, we observed toxic effect at a concentration of 100 µM and above. At 50 µM concentration, EPS showed better antioxidant activity against H₂O₂ (100 µM)-induced cytotoxicity, ROS formation and mitochondrial membrane damage in retinoic acid-differentiated SH-SY5Y cell line. Furthermore, our study revealed that 50 µM of EPS concentration reduced the glycogen synthase kinase-3 β (GSK3-β) expression and total tau protein level in H₂O₂ (100 µM)-treated cells. Findings from this study confirms the therapeutic efficacy of EPS on regulating Alzheimer's disease (AD) by regulating GSK3-β and total tau proteins phosphorylation, which helped to restore the cellular viability. This process could also reduce toxic fibrillary tangle formation and disease progression of AD. Therefore, it is our view that an optimal concentration of EPS therapy could decrease AD pathology by reducing tau phosphorylation through regulating the expression level of GSK3-β.

• Journal of Microbiology and Biotechnology
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• 제23권2호
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• pp.161-166
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• 2013

At present, acetylcholinesterase (AChE) inhibitors are the first group of drugs to treat mild to moderate Alzheimer's disease (AD). Although beneficial in improving cognitive and behavioral symptoms, the effectiveness of AChE inhibitors has been questioned since they do not delay or prevent neurodegeneration in AD patients. Therefore, in the present study, in order to develop new and effective anti-AD agents from lichen products, both the AChE inhibitory and the neuroprotective effects were evaluated. The AChE inhibitory assay was performed based on Ellman's reaction, and the neuroprotective effect was evaluated by using the MTT method on injured PC12 cells. One AChE inhibitor ($IC_{50}$ = 27.1 ${\mu}g/ml$) was isolated by means of bioactivity-guided isolation from the extract of lichen-forming fungus Cladonia macilenta, which showed the most potent AChE inhibitory activity in previous screening experiment. It was then identified as biruloquinone by MS, and $^1H$- and $^{13}C$-NMR analyses. The inhibitory kinetic assay suggested that biruloquinone is a mixed-II inhibitor on AChE. Meanwhile, biruloquinone improved the viability of the $H_2O_2$- and ${\beta}$-amyloid-injured PC12 cells at 1 to 25 ${\mu}g/ml$. The protective effects are proposed to be related to the potent antioxidant activities of biruloquinone. These results imply that biruloquinone has the potential to be developed as a multifunctional anti- AD agent.

• Korean Journal of Radiology
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• 제24권11호
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• pp.1131-1141
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• 2023

Objective: Cortical iron deposition has recently been shown to occur in Alzheimer's disease (AD). In this study, we aimed to evaluate how cortical gray matter iron, measured using quantitative susceptibility mapping (QSM), differs in the clinical cognitive impairment spectrum. Materials and Methods: This retrospective study evaluated 73 participants (mean age ± standard deviation, 66.7 ± 7.6 years; 52 females and 21 males) with normal cognition (NC), 158 patients with mild cognitive impairment (MCI), and 48 patients with AD dementia. The participants underwent brain magnetic resonance imaging using a three-dimensional multi-dynamic multi-echo sequence on a 3-T scanner. We employed a deep neural network (QSMnet+) and used automatic segmentation software based on FreeSurfer v6.0 to extract anatomical labels and volumes of interest in the cortex. We used analysis of covariance to investigate the differences in susceptibility among the clinical diagnostic groups in each brain region. Multivariable linear regression analysis was performed to study the association between susceptibility values and cognitive scores including the Mini-Mental State Examination (MMSE). Results: Among the three groups, the frontal (P < 0.001), temporal (P = 0.004), parietal (P = 0.001), occipital (P < 0.001), and cingulate cortices (P < 0.001) showed a higher mean susceptibility in patients with MCI and AD than in NC subjects. In the combined MCI and AD group, the mean susceptibility in the cingulate cortex (β = -216.21, P = 0.019) and insular cortex (β = -276.65, P = 0.001) were significant independent predictors of MMSE scores after correcting for age, sex, education, regional volume, and APOE4 carrier status. Conclusion: Iron deposition in the cortex, as measured by QSMnet+, was higher in patients with AD and MCI than in NC participants. Iron deposition in the cingulate and insular cortices may be an early imaging marker of cognitive impairment related neurodegeneration.

• Investigative Magnetic Resonance Imaging
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• 제25권3호
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• pp.164-171
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• 2021

Purpose: Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease (AD). Brain atrophy in this disease spectrum begins in the medial temporal lobe structure, which can be recognized by magnetic resonance imaging. To overcome the unsatisfactory inter-observer reliability of visual evaluation, quantitative brain volumetry has been developed and widely investigated for the diagnosis of MCI and AD. The aim of this study was to assess the prediction accuracy of quantitative brain volumetry using a fully automated segmentation software package, NeuroQuant^®, for the diagnosis of MCI. Materials and Methods: A total of 418 subjects from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease cohort were included in our study. Each participant was allocated to either a cognitively normal old group (n = 285) or an MCI group (n = 133). Brain volumetric data were obtained from T1-weighted images using the NeuroQuant software package. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to investigate relevant brain regions and their prediction accuracies. Results: Multivariate logistic regression analysis revealed that normative percentiles of the hippocampus (P < 0.001), amygdala (P = 0.003), frontal lobe (P = 0.049), medial parietal lobe (P = 0.023), and third ventricle (P = 0.012) were independent predictive factors for MCI. In ROC analysis, normative percentiles of the hippocampus and amygdala showed fair accuracies in the diagnosis of MCI (area under the curve: 0.739 and 0.727, respectively). Conclusion: Normative percentiles of the hippocampus and amygdala provided by the fully automated segmentation software could be used for screening MCI with a reasonable post-processing time. This information might help us interpret structural MRI in patients with cognitive impairment.

• BMB Reports
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• 제57권6호
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• pp.281-286
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• 2024

Adult hippocampal neurogenesis plays a pivotal role in maintaining cognitive brain function. However, this process diminishes with age, particularly in patients with neurodegenerative disorders. While small, non-coding microRNAs (miRNAs) are crucial for hippocampal neural stem (HCN) cell maintenance, their involvement in neurodegenerative disorders remains unclear. This study aimed to elucidate the mechanisms through which miRNAs regulate HCN cell death and their potential involvement in neurodegenerative disorders. We performed a comprehensive microarray-based analysis to investigate changes in miRNA expression in insulin-deprived HCN cells as an in vitro model for cognitive impairment. miR-150-3p, miR-323-5p, and miR-370-3p, which increased significantly over time following insulin withdrawal, induced pronounced mitochondrial fission and dysfunction, ultimately leading to HCN cell death. These miRNAs collectively targeted the mitochondrial fusion protein OPA1, with miR-150-3p also targeting MFN2. Data-driven analyses of the hippocampi and brains of human subjects revealed significant reductions in OPA1 and MFN2 in patients with Alzheimer's disease (AD). Our results indicate that miR-150-3p, miR-323-5p, and miR-370-3p contribute to deficits in hippocampal neurogenesis by modulating mitochondrial dynamics. Our findings provide novel insight into the intricate connections between miRNA and mitochondrial dynamics, shedding light on their potential involvement in conditions characterized by deficits in hippocampal neurogenesis, such as AD.

• Food Science and Biotechnology
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• 제17권2호
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• pp.384-388
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• 2008

Alzheimer's disease (AD) is the most common neurodegenerative disorder and is responsible for more than 50% of all dementia cases. There is significant interest in finding new sources of compounds that inhibit acetylcholinesterase (AChE) to be used in the treatment of AD, since only a few AChE inhibitors, such as galanthamine, physostigmine, and tacrine, are available for clinical use. In the present study, ICR mice were treated with a 1 mg/kg scopolamine, which caused impaired cognitive ability. The steady consumption of a water extract of Chrysanthemum indicum Linne flowers for 3 months significantly prevented the scopolamine induced deficit of the spatial cognitive capability of mice. It also improved long-term memory in mice with amnesia induced by scopolamine, as assessed by the Morris water maze and passive avoidance tests. In addition, water extract consumption significantly decreased AChE activity in mouse brain, leading to inhibition of acetylcholine hydrolysis.