• Journal of Embryo Transfer
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• v.25 no.1
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• pp.35-42
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• 2010

Many studies propose that dysfunction of mitochondrial proton-translocating NADH-ubiquinone oxidoreductase (complex I) is associated with neurodegenerative disorders, such as Parkinson's disease and Huntington's disease. Mammalian mitochondrial proton-translocating NADH-quinone oxidoreductase (complex I) consists of at least 46 different subunits. In contrast, the NDI1 gene of Saccharomyces cerevisiae is a single subunit rotenone-insensitive NADH-quinone oxidoreductase that is located on the matrix side of the inner mitochondrial membrane. With a recombinant adeno-associated virus vector carrying the NDI1 gene (rAAV-NDI1) as the gene delivery method, we were able to attain high transduction efficiencies even in the human epithelial cervical cancer cells that are difficult to transfect by lipofection or calcium phosphate precipitation methods. Using a rAAV-NDI1, we demonstrated that the Ndi1 enzyme is successfully expressed in HeLa cells. The expressed Ndi1 enzyme was recognized to be localized in mitochondria by confocal immunofluorescence microscopic analyses and immunoblotting. Using digitonin-permeabilized cells, it was shown that the NADH oxidase activity of the NDI1-transduced HeLa cells were not affected by rotenone which is inhibitor of complex I, but was inhibited by flavone and antimycin A. The NDI1-transduced cells were able to grow in media containing rotenone. In contrast, control cells that did not receive the NDI1 gene failed to survive. In particular, in the NDI1-transduced cells, the yeast enzyme becomes integrated into the human respiratory chain. It is concluded that the NDI1 gene provides a potentially useful tool for gene therapy of mitochondrial diseases caused by complex I deficiency.

• Journal of Acupuncture Research
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• v.33 no.1
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• pp.117-125
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• 2016

Objectives : The purpose of this report is to introduce a rare case of a patient with Chorea Hyperglycemia Basal Ganglia syndrome (C-H-BG) whose initial medical interventions were started 2 weeks after the onset, and to suggest the possibility of treatment using a combined Western-Korean medicine approach. Methods : A 75-year-old female C-H-BG patient complaining of persistent right-sided hemichorea was treated with a therapy that combined Korean and Western medicine from April 4, 2015 to April 29, 2015. Improvements of symptoms were measured by a motor assessment of Unified Huntington's Disease Rating Scale (UHDRS), Visual Analog Scale (VAS) and the number of involuntary movements. Results : Motor assessment of UHDRS, VAS and the number of involuntary movements all showed a gradually improving tendency during 26 days of admission treatment. However, the patient's hemichorea persisted. Conclusion : Rapid blood sugar control is the most important treatment for C-H-BG, because pathologic changes of basal ganglia seem to become irreversible as time goes by. A combined Western-Korean medicine approach to treating C-H-BG seems effective not only in reducing hemichorea, but also in the management of accompanying symptoms such as muscle pain and general weakness.

• Advances in Traditional Medicine
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• v.10 no.4
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• pp.239-253
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• 2010

Coenzyme $Q_{10}$ ($CoQ_{10}$, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of $CoQ_{10}$ in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit in $CoQ_{10}$ status has been determined in a number of neuromuscular and neurodegenerative disorders. Primary disorders of $CoQ_{10}$ biosynthesis are potentially treatable conditions and therefore a high degree of clinical awareness about this condition is essential. A secondary loss of $CoQ_{10}$ status following HMG-CoA reductase inhibitor (statins) treatment has been implicated in the pathophysiology of the myotoxicity associated with this pharmacotherapy. $CoQ_{10}$ and its analogue, idebenone, have been widely used in the treatment of neurodegenerative and neuromuscular disorders. These compounds could potentially play a role in the treatment of mitochondrial disorders, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Friedreich's ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of $CoQ_{10}$, as well as the rationale and the role in clinical practice of $CoQ_{10}$ supplementation in different neurological diseases, from primary $CoQ_{10}$ deficiency to neurodegenerative disorders. These will help in future for treatment of patients suffering from neurodegenerative disease.

• Reproductive and Developmental Biology
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• v.35 no.4
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• pp.427-434
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• 2011

Mitochondria diseases have been reported to involve structural and functional defects of complex I-V. Especially, many of these diseases are known to be related to dysfunction of mitochondrial proton-translocating NADH-ubiquinone oxidoreductase (complex I). The dysfunction of mitochondria complex I is associated with neurodegenerative disorders, such as Parkinson's disease, Huntington's disease, and Leber's hereditary optic neuropathy (LHON). Mammalian mitochondrial proton-translocating NADH-quinone oxidoreductase (complex I) is largest and consists of at least 46 different subunits. In contrast, the NDI1 gene of Saccharomyces cerevisiae is a single subunit rotenone-insensitive NADH-quinone oxidoreductase that is located on the matrix side of the inner mitochondrial membrane. The Saccharomyces cerevisiae NDI1 gene using a recombinant adeno-associated virus vector (rAAV-NDI1) was successfully expressed in AML12 mouse liver hepatocytes and the NDI1-transduced cells were able to grow in media containing rotenone. In contrast, control cells that did not receive the NDI1 gene failed to survive. The expressed Ndi1 enzyme was recognized to be localized in mitochondria by confocal immunofluorescence microscopic analyses and immunoblotting. Using digitonin-permeabilized cells, it was shown that the NADH oxidase activity of the NDI1-transduced cells was not affected by rotenone which is inhibitor of complex I, but was inhibited by antimycin A. Furthermore, these results indicate that Ndi1 can be functionally expressed in the AML12 mouse liver hepatocytes. It is conceivable that the NDI1 gene is powerful tool for gene therapy of mitochondrial diseases caused by complex I deficiency. In the future, we will attempt to functionally express the NDI1 gene in mouse embryonic stem (mES) cell.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.210-217
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• 2018

Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer's disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3',4'-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3',4'-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin $E_2$ and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor $(NF)-{\kappa}B$ activation. This indicates that the anti-inflammatory activities of 3',4'-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and $NF-{\kappa}B$ signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3',4'-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.

• Journal of Life Science
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• v.23 no.1
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• pp.125-130
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• 2013

Calponin 3 is an F-actin-binding protein and plays a key role in regulating spine plasticity and synaptic activity in neurons. Unlike the other subtypes, calponin 1 and 2, which are expressed in smooth and cardiac muscle cells, calponin 3 is highly expressed in the brain. The goal of this study was to elucidate the spatiotemporal expression pattern of calponin 3 following repeated administration of 3-nitropropionic acid in mice. The repeated administration of 3-nitropropionic acid generated necrotic neuronal cell death in the striatum. Calponin 3 was up-regulated in the neuroprotective penimbral region from 1.5 days after the last injection and thereafter. Double immunofluorescence study revealed that calponin 3 was induced in GFAP-positive astrocytes. These results suggest that calponin 3 induction in the neuroprotective penumbral area following 3-nitropropionic acid intoxication may play a key role in reactive astrogliosis in the striatum.

• KSBB Journal
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• v.18 no.3
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• pp.207-210
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• 2003

The locus coeruleus (LC) contains about half of the total number of noradrenergic neurons in the brain and those noradrenergic neurons from the LC innervate entire brain regions. The LC is a major common target region in several neurodegenerative disorders such as Alzheimer's, Pakinson's and Huntington's diseases. The brain-derived neurotrophic factor (BDNF) regulate neuronal cell survival and differentiation of central nervous system neurons, including LC noradrenergic neurons. In this study, various small molecules and growth factors were tested as candidates to promote the production of BDNF in LC noradrenergic neuronal cells. The molecules tested include neuropeptides, cytokines, growth factors, neurotransmitters, and intracellular signaling agents. Four small molecules or growth factors, FGF8b, BMP-4, forskolin, and dibutyryl cGMP, were found to increase the release of BDNF in LC noradrenergic neurons. Especially, BMP-4 significantly enhanced BDNF production over 2.5-fold in LC noradrenergic neurons.

• Magazine of the Korean Society of Agricultural Engineers
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• v.29 no.4
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• pp.106-116
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• 1987

미국 Utah주의 huntington 화력발전소에서 냉각수를 사용하고 버리는 염분농도가 4mmhos/cm 정도로 높아 자연하천으로 그대로 방류 시킬 수 없으며, 미 환경법에 따라 안전처리후 방류할 수 있다. 따라서 이 염분발생 처리방법의 하나로 보리, 밀, 옥수수, 감자 그리고 알팔파등 사료작물의 관개용수로 이용할 수 있는 방법이 장기간 시험연구되고 있다. 현재로서는 이 방법이 경제적인 것으로 평가되고 있으나 장기적으로 이 염분폐수로 인한 토양의 성질변화 작용의 생산량 감소등에 미치는 영향을 구명하기 위해서 1977년에 시작하여 8년 연속 연구사업으로 진행되고 있다. 본 논문에서는 지난 8년간(1977~1984년)의 관측.조사자료를 이용하여 염분 관개용수가 장기적으로 생산량 추정과 계획예측을 위한 자발성과 토양수분변화를 추정할 수 있는 모형에 의하여 연구한 결과를 요약하면 다음과 같다. 1. EC 4mmhos/cm의 염분 관개용수로 8년간 장기간 추출한 결과, 추출용수의 양에 관계내 염분축적은 예상보다 서서히 진행되었으며, 이 염분축적이 작물의 생산량 감소의 주원인은 아니었다. 2. 지난 2년간의 관측 결과, 염분 관개용수에 함유된 10ppm정도의 요소가 작물 특히 보리, 옥수수, 감자등의 생산량 감소의 주원인 것으로 판단된다. 염분용수 진개구에는 하천수 보다 20배가 많은 요소가 축적돼 있었으며, 이는 요소가 토양내에 잘 침투되며, 토양으로 부터 요소를 용달시키려는 염분을 용달시킬 때 보다 후러씬 더 많은 용달용수를 필요로함을 뜻한 작물들의 면요소성을 구명하기위한 모형개발이 요구된다. 3. 염분관개용수로 관개할 때 보리, 옥수수, 감자등의 작물 생산량과 풍작물 생산량은 현저하게 감소하였다. 보리, 옥수수의 염분용수에 의한 생산량과 하천수에 의한 생산량과의 비는 풍건물의 경우 0.6, 매물의 경우 0.5였으며 감자의 경우는 0.2이하였다. 4. 염분용수 관개구와 하천수 관개구의 모든작물에서 풍건물 생산량과 축배량 사이에는 강한 직선적인 관계를 보였다. 보리, 감자의 작물 생산량과 축배량사이에도 선형의 관계가 성립되었으나, 밀과 옥수수의 매물 생산량과 축배량사이에는 곡선적인 관계를 나타내었다.

• Korean Journal of Biological Psychiatry
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• v.27 no.2
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• pp.42-57
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• 2020

Electroconvulsive therapy (ECT) is indicated for various mental disorders (e.g., major depressive disorder, schizophrenia, and bipolar disorder) and the behavioral and psychological symptoms of dementia in elderly patients. Furthermore, ECT is a useful first-line treatment in emergency and crisis situations such as suicide risk, violent behavior, catatonia, and food refusal, which are more frequent in elderly patients. ECT is also effective in the treatment of the motor symptoms of neurological disorders, such as Parkinson's disease and Huntington's disease. Due to the high risk of various physical diseases, the comorbid physical conditions of elderly patients should be individually controlled to optimize ECT treatment. Compared to young adults, in elderly patients the seizure threshold is higher, the seizure duration is shorter, and the anesthetic dose is lower. On the contrary, the response rate in the elderly is both faster and higher. Considering potential cognitive decline and the prevention of further deterioration of cognitive function in elderly patients, in the absence of significant comorbidities, twice weekly sessions and right unilateral electrode placement with a lower seizure threshold and less cognitive effect are preferred to bilateral electrode placement, which has a high risk of adverse cognitive effects. After an acute course of ECT, continuation and maintenance of ECT, combined with prescription of therapeutic drugs, may prevent possible relapse or recurrence of mental disorders. In conclusion, ECT can be used to treat mental disorders in elderly adults, with safety and effectiveness comparable to that in young adults.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.390-399
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• 2023

Background: Gintonin (GT), a Panax ginseng-derived lysophosphatidic acid receptor (LPAR) ligand, has positive effects in cultured or animal models for Parkinson's disease, Huntington's disease, and so on. However, the potential therapeutic value of GT in treating epilepsy has not yet been reported. Methods: Effects of GT on epileptic seizure (seizure) in kainic acid [KA, 55mg/kg, intraperitoneal (i.p.)]-induced model of mice, excitotoxic (hippocampal) cell death in KA [0.2 ㎍, intracerebroventricular (i.c.v.)]-induced model of mice, and levels of proinflammatory mediators in lipopolysaccharide (LPS)-induced BV2 cells were investigated. Results: An i.p. injection of KA into mice produced typical seizure. However, it was significantly alleviated by oral administration of GT in a dose-dependent manner. An i.c.v. injection of KA produced typical hippocampal cell death, whereas it was significantly ameliorated by administration of GT, which was related to reduced levels of neuroglial (microglia and astrocyte) activation and proinflammatory cytokines/enzymes expression as well as increased level of the Nrf2-antioxidant response via the upregulation of LPAR 1/3 in the hippocampus. However, these positive effects of GT were neutralized by an i.p. injection of Ki16425, an antagonist of LPA1-3. GT also reduced protein expression level of inducible nitric-oxide synthase, a representative proinflammatory enzyme, in LPS-induced BV2 cells. Treatment with conditioned medium clearly reduced cultured HT-22 cell death. Conclusion: Taken together, these results suggest that GT may suppress KA-induced seizures and excitotoxic events in the hippocampus through its anti-inflammatory and antioxidant activities by activating LPA signaling. Thus, GT has a therapeutic potential to treat epilepsy.