• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.327-332
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• 2019

Alzheimer's disease (AD) is a common neurodegenerative disease. Oxidative stress by amyloid beta peptide (Aβ) of neuronal cell is the most cause of AD. In the present study, protective effects of several flavonoids such as kaempferol (K), kaempferol-3-O-glucoside (KG), quercetin (Q) and quercetin-3-β-ᴅ-glucoside (QG) from Aβ_25-35 were investigated using C6 glial cell. Treatment of Aβ_25-35 to C6 glial cell showed decrease of cell viability, while treatment of flavonoids such as Q and QG increased cell viability. In addition, treatment of flavonoids declined reactive oxygen species (ROS) production compared with Aβ_25-35-induced control. The ROS production was increased by treatment of Aβ_25-35 to 133.39%, while KG and QG at concentration of 1 μM decreased ROS production to 107.44 and 113.10%, respectively. To study mechanisms of protective effect of these flavonoids against Aβ_25-35, the protein expression related to inflammation under Aβ_25-35-induced C6 glial cell was investigated. The results showed that C6 glial cell under Aβ_25-35-induced oxidative stress up-regulated inflammation-related protein expressions. However, treatment of flavonoids led to reduction of protein expression such as inducible nitric oxide synthase, cyclooxygenase-2 and interleukin-1β. Especially, treatment of KG and QG decreased more effectively inflammation-related protein expression than its aglycones, K and Q. Therefore, the present results indicated that K, Q and its glycosides attenuated Aβ_25-35-induced neuronal oxidative stress and inflammation.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.1
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• pp.25-30
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• 2023

Leigh syndrome is a rare progressive neurodegenerative mitochondrial disorder with clinical and genetic heterogeneity. Recently, balletic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes from Leigh and West syndrome to a rare syndrome CAGSSS characterized by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia syndrome (OMIM#616007). We describe a child with Korean Leigh syndrome with urologic manifestations resulting from a compound heterozygote mutation in IARS2. A 5-year-old girl visited the emergency room with a complaint of abdominal pain accompanied by abdominal distension. Abdominal-pelvic CT showed a markedly distended urinary bladder without definite obstructive lesions. She was diagnosed with neurogenic bladder dysfunction based on a urodynamic study. She had global delayed development due to neurologic regression after 6 months of age and a history of bilateral cataract surgery at the age of 2 years. Her brain magnetic resonance imaging showed symmetrically increased signal intensities in the bilateral putamen and caudate nuclei with diffuse cerebral atrophy. No gene variants were identified through whole-mitochondrial genome analysis. Whole exome sequencing was performed for diagnosis, and compound heterozygous pathogenic variants were identified in IARS2: c.2446C>T (p. Arg816Ter) and c.2450G>A (p. Arg817His). To the best of our knowledge, this is the first case report of bladder dysfunction manifestation in a patient with IARS2-related Leigh syndrome. Thus, it broadens the clinical and genetic spectrum of IARS2-associated diseases.

• Journal of Genetic Medicine
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• v.16 no.2
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• pp.55-61
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• 2019

Purpose: Genetic defects in the nuclear-encoded mitochondrial aminoacyl-tRNA synthetases were first identified as causes of various disorders in 2007. Variants in IARS2, which encodes a mitochondrial isoleucyl-tRNA synthetase, were first reported in 2014. These variants are associated with diverse phenotypes ranging from CAGSSS (CAtaracts, Growth hormone deficiency, Sensory neuropathy, Sensorineural hearing loss, and Skeletal dysplasia) and Leigh syndrome to isolated nonsyndromic cataracts. Here, we describe the phenotypic and genetic spectrum of Korean patients with IARS2-related disorders. Materials and Methods: Using whole-exome sequencing followed by Sanger sequencing, we identified five patients with IARS2 mutations. Their medical records and brain magnetic resonance images were reviewed retrospectively. Results: All five patients presented with developmental delay or regression before 18 months of age. Three patients had bilateral cataracts, but none had hearing loss or sensory neuropathy. No evidence of skeletal dysplasia was noted, but two had short stature. One patient had cardiomyopathy and another exhibited renal tubulopathy and hypoparathyroidism. Their brain imaging findings were consistent with Leigh syndrome. Interestingly, we found the recurrent mutations p.R817H and p.V105Dfs*7 in IARS2. Conclusion: To our knowledge, this is the first report of Korean patients with IARS2-related disorders. Our findings broaden the phenotypic and genotypic spectrum of IARS2-related disorders in Korea and will help to increase clinical awareness of IARS2-related neurodegenerative diseases.

• Korean Journal of Food Science and Technology
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• v.41 no.6
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• pp.712-716
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• 2009

In this study, the antioxidant and neuronal cell protective effects of methanol extract from Schizandra chinensis were evaluated. The proximate composition and total phenolics content of the extract were as follows: 64.88% nitrogen free extract, 10.56% crude fiber, 10.22% moisture, 8.33% crude protein, 5.05% ash, 0.96% crude fat, and 83.04 mg/g of total phenolics. In assays the methanol extract of Schizandra chinensis presented ferric reducing/antioxidant power (FRAP) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity in a dose-dependent manner. In a cell viability assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT), the methanol extract showed protective effect against $H_2O_2$-induced neurotoxicity, and lactate dehydrogenase (LDH) release into medium was also inhibited by various concentrations of extracts (68-80%). Cell viability after treatment of the methanol extract was higher than that shown for vitamin C ($100\;{\mu}M$) using a neutral red uptake (NRU) assay. Therefore, these data suggest that the methanol extract of Schizandra chinensis may be useful for neurodegenerative diseases including Alzheimer's disease.

• Progress in Medical Physics
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• v.29 no.1
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• pp.29-41
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• 2018

The objective of this study was to evaluate the chemical exchange saturation transfer (CEST) effect of amino acids and neurotransmitters, which exist in the human brain, depending on the concentration, pH, and amplitude of the saturation radiofrequency field. Phantoms were developed with asparagine (Asn), ${\gamma}-aminobutyric$ acid (GABA), glutamate (Glu), glycine (Gly), and myoinositol (MI). Each chemical had three different concentrations of 10, 30, and 50 mM and three different pH values of 5.6, 6.2, and 7.4. Full Z-spectrum CEST images for each phantom were acquired with a continuous-wave radiofrequency (RF) saturation pulse with two different $B_1$ amplitudes of $2{\mu}T$ and $4{\mu}T$ using an animal 9.4T MRI system. A voxel-based CEST asymmetry was mapped to evaluate exchangeable protons based on amide (-NH), amine ($-NH_2$), and hydroxyl (-OH) groups for the five target molecules. For all target molecules, the CEST effect was increased with increasing concentration and B1 amplitude; however, the CEST effect with varying pH displayed a different trend depending on the characteristics of the molecule. On CEST asymmetric maps, Glu and MI were well visualized around 3.0 and 0.9 ppm, respectively, and were well separated macroscopically at a pH of 7.4. The exchange rates of Asn, Glu, BABA, and Gly usually decreased with increasing pH. The CEST effect was dependent on the concentration, acidity of the target molecules, and B1 amplitude of the saturation RF pulse. The CEST effect for Asn can be observed in a 9.4T MRI system. The results of this study are based on applying the CEST technique in patients with neurodegenerative diseases when proteins in the brain are increased with disease progression.

• Korean Journal of Environmental Biology
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• v.24 no.2 s.62
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• pp.166-171
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• 2006

To elucidate the effect of phytoestrogens on the prevention of neurodegenerative disease in postmenopausal women, the expression of occludin which build up the blood-brain barrier was examined in hippocampus following oral administration of estrogen (E2), genistein, diadzein or combination of genistein and diadzein in ovariectomized (OVX) female rats. E2 significantly increased occludin mRNA level in OVX rat hippocampus, suggesting that estrogen is a physiological regulator for structural integrity of the blood-brain barrier in hippocampus. Following isoflavone diet for 4 weeks, there was significant increase in occludin mRNA level in hippocampus, suggesting that isoflavone diet may be effective for protection of structural integrity of blood-brain barrier in hippocampus from degenerative changes in estrogen deficiency.

• Journal of Life Science
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• v.30 no.6
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• pp.513-521
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• 2020

B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) is a polycomb group protein and a core component of polycomb repressive complex 1. Initial research into Bmi1 has focused on its role in tumorigenesis, and it is generally accepted that it is important for the proliferation and survival of cancer cells. However, more recent studies have revealed that Bmi1 is downregulated in brains with neurodegenerative disease and that it regulates the function of mitochondria and reactive oxygen species levels. In this study, we tested the therapeutic potential of Bmi1 in pilocarpine-induced seizures in Bmi1-knockout mice. Bmi1 expression transiently increased in the hippocampal CA1 and CA3 and the dentate gyrus following pilocarpine-induced status epilepticus (SE). In terms of seizure behavior, SE induction was 43.14% and 53.57% for Bmi1^+/+ and Bmi1^+/- mice, respectively. However, there was no significant difference in mortality or hippocampal damage between the two groups. Two months after SE induction, the frequency of epileptic seizures in the Bmi1^+/- mice was 50% lower than in the control group, although the difference was not statistically significant. In addition, mossy fiber outgrowth in the Bmi1^+/- mice was significantly higher than in their wild-type littermates. Taken together, these data indicate that reduced Bmi1 activity increases pilocarpine-induced seizure probability and mossy fiber outgrowth.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.4
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• pp.595-599
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• 2013

Alzheimer's disease is a progressive neurodegenerative disorder characterized by a gradual decline in memory associated with shrinkage of brain tissue, with a localized loss of neurons mainly in the hippocampus and basal forebrain. This study investigated the neuroprotective effect of Gastrodia elata aqueous extracts against scopolamine-induced neurotoxicity in the hippocampus of male Sprague-Dawley rats. The animals (n=25) were divided into five different groups with five animals per each group. The normal group (Nor) was administered with saline, while the control (Con) group was administered saline after scopolamine treatment. The experimental group (Exp) was administered Gastrodia elata aqueous extracts (200 mg/kg body weight) for 20 or 30 days after scopolamine treatment. From a light microscopy study, the nuclei of neurons in the hippocampus were more shrunken or condensed in the 20 or 30 day control groups compared to experimental groups. The densities of neurons from the CA1 and CA3 area of the hippocampus in the Exp increased compared with the Con. Amyloid ${\beta}$ protein, containing PAS-positive materials, was lower in the Exp compared with the Con. The present study demonstrates that Gastrodia elata aqueous extracts possess neuroprotective potential, thus validating its use in alleviating the toxic effects of scopolamine.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.18 no.12
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• pp.352-358
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• 2017

Frontotemporal dementia, the second most common cause of early onset dementia, is a neurodegenerative clinical syndrome characterized by progressive deficits in behavior, executive function and language. Although motor symptoms in frontotemporal dementia are represented by motor neuron disease, parkinsonism and progressive supranuclear palsy syndrome, there have been no reports of motor weakness caused by the direct involvement of central motor nervous systems in frontotemporal dementia. Moreover, no association between clinical dementia groups and complex regional pain syndrome has been reported. We diagnosed a rare case with motor weakness and complex regional pain syndrome of lower limbs due to central nervous system lesion in a patient with frontotemporal dementia by magnetic resonance imaging, electrodiagnostic study and three phase bone scan. Following steroid therapy for complex regional pain syndrome, pain was improved. Functional improvement was noted after rehabilitation therapy, including functional electrical stimulation, muscle strengthening exercise and gait training during hospitalization. This case report suggests that rehabilitation therapy for motor weakness in frontotemporal dementia could be effective for improving overall function.

• Nutrition Research and Practice
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• v.12 no.3
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• pp.191-198
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• 2018

BACKGROUD/OBJECTIVES: Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. MATERIALS/METHODS: C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. RESULTS: There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B ($NF{\kappa}B$) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. CONCLUSIONS: The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.