• Journal of Genetic Medicine
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• v.12 no.1
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• pp.38-43
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• 2015

Purpose: Spinocerebellar ataxias (SCAs) are progressive neurodegenerative disorders with diverse modes of inheritance. There are several subtypes of SCAs. SCA 8, SCA 12, and SCA 17 are the less common forms of SCAs with limited information available on their epidemiological profiles in Korea. The purpose of this study was to investigate the prevalence of SCA8, SCA12, and SCA17 in Korea. Materials and Methods: Ninety-six unrelated Korean patients were enrolled and showed normal trinucleotide repeats through polymerase-chain reaction (PCR) for the genes ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7, which correspond to SCA1, SCA2, SCA3, SCA6, and SCA7, respectively. PCR products from patients were further analyzed by capillary electrophoresis using fluorescence labeled primers for the genes ATXN8OS, PPP2R2B, and TBP, which correspond to SCA8, SCA12, and SCA17. Results: Three patients had 104, 97, and 75 abnormal expanded repeats in the ATXN8OS gene, the causative gene for SCA8. None of the patients exhibited abnormal repeats in SCA12 and SCA17. Normal trinucleotide repeat ranges of the cohort in this study were estimated to be 17-34 copies (average, $24{\pm}4copies$) for SCA8, 7-18 copies (average, $13{\pm}3copies$) for SCA12, and 26-43 copies (average, $35{\pm}2copies$) for SCA17. Conclusion: This study demonstrated that SCA8, SCA12, and SCA17 are rare in Korean patients with SCA, and further genetic studies are warranted to enhance the mutation detection rate in the Korean SCA population.

• Nutrition Research and Practice
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• v.12 no.3
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• pp.199-207
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• 2018

BACKGROUND/OBJECTIVES: Fermented Laminaria japonica (FL), a type sea tangle used as a functional food ingredient, has been reported to possess cognitive improving properties that may aid in the treatment of common neurodegenerative disorders, such as dementia. MATERIALS/METHODS: We examined the effects of FL on scopolamine (Sco)- and ethanol (EtOH)-induced hippocampus-dependent memory impairment, using the Passive avoidance (PA) and Morris water maze (MWM) tests. To examine the underlying mechanisms associated with neuroprotective effects, we analyzed acetylcholine (ACh) and acetylcholinesterase (AChE) activity, brain tissue expression of muscarinic acetylcholine receptor (mAChR), cAMP response element binding protein (CREB) and extracellular signal-regulated kinases 1/2 (ERK1/2), and immunohistochemical analysis, in the hippocampus of mice, compared to current drug therapy intervention. Biochemical blood analysis was carried out to determine the effects of FL on alanine transaminase (ALT), aspartate transaminase (AST), and triglyceride (TG) and total cholesterol (TC) levels. 7 groups (n = 10) consisted of a control (CON), 3 Sco-induced dementia and 3 EtOH-induced dementia groups, with both dementia group types containing an untreated group (Sco and EtOH); a positive control, orally administered donepezil (Dpz) (4mg/kg) (Sco + Dpz and EtOH + Dpz); and an FL (50 mg/kg) treatment group (Sco + FL50 and EtOH + FL50), orally administered over the 4-week experimental period. RESULTS: FL50 significantly reduced EtOH-induced increase in AST and ALT levels. FL50 treatment reduced EtOH-impaired step-through latency time in the PA test, and Sco- and EtOH-induced dementia escape latency times in the MWM test. Moreover, anticholinergic effects of Sco and EtOH on the brain were reversed by FL50, through the attenuation of AChE activity and elevation of ACh concentration. FL50 elevated ERK1/2 protein expression and increased p-CREB (ser133) in hippocampus brain tissue, according to Western blot and immunohistochemistry analysis, respectively. CONCLUSION: Overall, these results suggest that FL may be considered an efficacious intervention for Sco- and EtOH-induced dementia, in terms of reversing cognitive impairment and neuroplastic dysfunction.

• 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.

• Journal of Genetic Medicine
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• v.4 no.1
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• pp.84-87
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• 2007

Spinocerebellar Ataxia Type 3 (SCA 3) is a rare autosomal dominative disorder in which one of the neurodegenerative disorders is caused by a CAG repeat expansion on chromosome 14q32.1. The age at onset of disease is related to the size of the expanded CAG repeat. We present the prenatal diagnosis of SCA3 in a woman whose husband was known to carry an unstable CAG repeat expansion in the MJD gene. The diagnosis was made using PCR with a fluorescent probe for an expanded MJD allele. The normal ranges of (CAG)n of SCA3 are 14~38 repeats. The husband, who had a family history of SCA 3, has an expanded allele of 69 CAG repeats with a normal allele of 27 repeats. His wife had two normal alleles with 26 and 32 CAG repeats. The fetus had two normal alleles with 26 and 27 CAG repeats; consequently, the baby w as healthy. We report a case of prenatal diagnosis of SCA3 using a fluorescent PCR which is rapid and accurate.

• Journal of Life Science
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• v.15 no.6 s.73
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• pp.916-922
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• 2005

Parkin, known as an E3 ubiquitin ligase, has essential role in protein quality control, and its severe dysfunction leads to neurodegenerative disorders. Human Parkin was excessively degraded when expressed in Escherichia coli under the conventional induction condition ($37^{\circ}C$ culture condition with 0.5 mM IPTG). To optimize the induction and culture conditions for recombinant human Parkin and develop a rapid method for the Parkin purification, we expressed Parkin by using PCEX system at the different culture temperatures and IPTC concentrations. The intact Parkin protein was purified to approximately $90\%$ purity with suitable amounts of protein under the optimal culture condition ($25^{\circ}C$E with 0.01 mM IPTG). Additionally, we constructed various parkin plasmids with different tagging systems and investigated their expression patterns in HEK293 cells. We found that the proteolytically sensitive site is localized within a ubiquitin-like domain of Parkin. This study developes a method for generating useful reagents to investigate biochemical properties of Parkin.

• Journal of the Korean Child Neurology Society
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• v.25 no.3
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• pp.200-203
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• 2017

Spinocerebellar ataxias (SCAs) are autosomal dominant neurodegenerative disorders which disrupt the afferent and efferent pathways of the cerebellum that cause cerebellar ataxia. Spectrin beta non-erythrocytic 2 (SPTBN2) gene encodes the ${\beta}-III$ spectrin protein with high expression in Purkinje cells that is involved in excitatory glutamate signaling through stabilization of the glutamate transporter, and its mutation is known to cause spinocerebellar ataxia type 5. Three years and 5 months old boy with delayed development showed leukodystrophy and cerebellar atrophy in brain magnetic resonance imaging (MRI). Diagnostic exome sequencing revealed that the patient has heterozygous mutation in SPTBN2 (p.Glu1251Gln) which is a causative genetic mutation for spinocerebellar ataxia type 5. With the patient's clinical findings, it seems reasonable to conclude that p.Glu1251Gln mutation of SPTBN2 gene caused spinocerebellar ataxia type 5 in this patient.

• Food Science and Preservation
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• v.17 no.5
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• pp.720-726
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• 2010

The in vitro antioxidant activities and neuronal cell protective effects of 60% (w/v) methanolic extract from Houttuynia cordata were investigated. The contents of total phenolics and quercitrin in the extract were 17.71 mg/g and 75.80 ${\mu}g$/g, respectively. DPPH and ABTS radical-scavenging activities were 87.79% and 99.27%, respectively, when the extract was tested at 5 mg/ml. The FRAP (ferric reducing/antioxidant power) assay showed a dose-dependent increse in activity. In a cell viability assay using MTT, the extract protected against $H_2O_2$-induced neurotoxicity. Lactate dehydrogenase (LDH) leakage was also inhibited by the extract, as was lipid peroxidation as shown using the mouse brain homogenate test. These data indicate that a 60% (w/v) methanolic extract of Houttuynia cordata has in vitro antioxidant activities, and ingestion there of may reduce the risk of developing neurodegenerative disorders.

• Korean Journal of Plant Resources
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• v.23 no.2
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• pp.165-171
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• 2010

Oxidative stress induced by reactive oxygen intermediates has been implicated in a variety of human diseases including neurodegenerative disorders, cancer, cardiovascular and respiratory diseases, and mode of action of environmental toxicants. Tert-butylhydroperoxide (t-BHP) is an organic lipid hydroperoxide analogue, which is commonly used as a pro-oxidant for evaluating mechanisms involving oxidative stress in cells and tissues. In this study, the underlying mechanisms involved in the protective effects of Hwabuk 94 kiwifruit (Actinidia deliciosa cv. 'Hwabuk 94'), which is cultivated in Jeju, on the t-BHP-induced cytotoxicity in PC12 cell. The pretreatment of rat pheochromocytoma cell line PC12 with Hwabuk 94 extract ($1-100\;{\mu}g/ml$) resulted in a significant recovery from t-BHP-induced cell death and increased Bcl-2 and procaspase-3 expression, whereas the expression of Bax and cleaved PARP were decreased in a dose-dependent manner compared to the control. Furthermore, Hwabuk 94 inhibited the t-BHP-induced p38 MAP kinase and extracellular signal-regulated kinase 1/2, but not c-Jun N-terminal kinase activations. Finally, these findings suggest that Hwabuk 94 kiwifruit might attenuate t-BHP-induced PC12 cell cytotoxicity, at least in part, through the inhibition of signaling pathways mediated by the ERK1/2 and p38 MAP kinase.

• Journal of Life Science
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• v.29 no.9
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• pp.1034-1046
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• 2019

The mitochondria is the major cellular organelle of energy metabolism for the supply of cellular energy; it also plays an important role in controlling calcium regulation, reactive oxygen species (ROS) production, and apoptosis. Mitochondrial dysfunction causes various diseases, such as neurodegenerative diseases, Lou Gehrig's disease, cardiovascular disease, mental disorders, diabetes, and cancer. Most of the diseases are age-related diseases. In this review, we focus on the roles of mitochondrial dysfunction in cancer. Mitochondrial dysfunction induces carcinogenesis and is found in many cancers. The factors that cause mitochondrial dysfunction differ depending on the types of carcinoma, and those factors could cause cancer malignancy, such as resistance to therapy and metastasis. Mitochondrial dysfunction is caused by a lack of mitochondria, an inability to provide key substances, or a dysfunction in the ATP synthesis machinery. The main factor associated with cancer malignancy is mtDNA depletion. Mitochondrial dysfunction would leads to malignancy through changes in molecular activity or expression, but it is not known in detail which changes lead to cancer malignancy. In order to explore the relationship between mitochondrial dysfunction and cancer malignancy in detail, mitochondria dysfunctional cell lines are constructed using chemical methods such as EtBr treatment or gene editing methods, including shRNA and CRISPR/Cas9. Those mitochondria dysfunctional cell lines are used in the study of various diseases caused by mitochondrial dysfunction, including cancer.

• The Journal of Internal Korean Medicine
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• v.40 no.2
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• pp.220-227
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• 2019

Objectives: Parkinson's disease is the neurodegenerative disease that affects both motor and non-motor function, including postural instability. Camptocormia is an abnormal condition in which the thoracolumbar spine bends forward during walking or standing. However, the treatment options are limited and often not effective. The purpose of this study was to report on the Korean medical treatment of a Parkinson's disease patient with postural instability who presented with camptocormia. Methods: We used Korean medical treatment including herbal medicine (Jemageopung-tang), acupuncture and pharmacopuncture therapy to the patient who was admitted to the hospital for 21 days. The clinical symptoms were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS) and walking time without assistance. Results: After treatment, the UPDRS Parts 2 and 3 scores were decreased from 5 to 3 and 20 to 9, respectively. Also, the walking time without assistance was improved. Conclusion: This study suggested that Korean medical treatment could be an effective option for treating Parkinson's disease with postural instability.