• 한국방사선학회논문지
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• 제8권5호
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• pp.231-240
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• 2014

본 연구는 경도인지장애가 동반된 파킨슨병 환자에 대하여 인지 기능 평가를 위한 서울신경심리검사와 뇌 자기공명 영상에서 영역별 뇌실에 대한 체적 변화를 분석하여 경도인지장애가 동반된 파킨슨병에 대한 진단적 기준을 판단할 수 있는 가이드라인을 제시하고자 하였다. 이를 위하여 파킨슨병으로 진단 받은 환자(경도인지장애군: 34명, 비인지장애군: 34명)를 대상으로 주의력, 언어, 기억력, 시공간, 그리고 전두엽 집행 기능에 대한 서울신경심리검사와 뇌 자기공명영상 검사를 시행하였다. 또한 영역별 뇌실에 대한 체적 변화를 비교하기 위하여 정상인 32명(정상 대조군)을 추가 선정하여 추가적으로 뇌 자기공명영상 검사를 시행하였으며 영역별 뇌실에 대한 체적 분석은 프리서퍼(Freesurfer Ver. 5.1, Boston MA, USA)를 통해 수행되었다. 결과적으로 경도인지장애군은 시공간 및 기억력에 대한 수행 능력이 비인지장애군과 비교하여 통계적으로 유의하게 감소되었다(p<0.05). 영역별 뇌실에 대한 체적 변화는 좌 우측뇌실, 좌 우하측뇌실, 제3뇌실에서 통계적으로 유의한 체적 변화를 나타내었으며 객관화된 비교를 위하여 정규화한 백분율을 적용한 체적의 변화는 비인지장애군보다 경도인도장애군에서 확장되어 나타났다. 특히 경도인지장애를 동반한 파킨슨병 환자의 좌 우측뇌실의 확장은 서울신경심리검사에서 시공간 및 기억력 영역에 대하여 뚜렷한 양적 선형관계를 보였다(r>0.5, p<0.05). 따라서 뇌 자기공명영상에서 프리서퍼를 이용하여 영역별 뇌실의 체적 변화를 관찰하고 서울 신경심리검사와 상관관계를 분석함으로써 경도인지장애를 동반한 파킨슨병 환자의 진단적 기준을 마련할 수 있을 것으로 판단되었다.

• 대한물리의학회지
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• 제8권1호
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• pp.49-58
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• 2013

PURPOSE: The purpose of this study was to determine if auditory cues velocity has a greater effect on the gait pattern of patients with Parkinson's disease (PD) than the cues applied individually. METHODS: The subjects were 15 elderly patients diagnosed with PD, 15 healthy elderly persons. Patients were measured of three conditions performed in random order: slow, general, fast. The auditory cue velocity consisted of a metronome beat ${\pm}20%$ than the subject's general gait speed. Using a motion analysis and a force platform measurement system, changes in spatiotemporal variables, kinetic and kinematic variables were compared to gait analysis. RESULTS: Comparison between the auditory cues velocity, there was a significant difference in the spatiotemporal variables with regard to the cadence, stride length, support time, step length, double support time (p<.05). Comparison between the auditory cues velocity, there was a significant increase general and fast velocity gait than slow velocity gait in the maximum flexion in swing phase of knee joint (p<.05). There appears to be the aspect of an increasing ground reaction force (GRF) on the first peak in the vertical axis (p<.05). CONCLUSION: Auditory cues velocity improved of spatio-temporal factors, kinematic and kinetic factors depending on the velocity of the faster. Therefore at the rehabilitation training of PD patients auditory cues velocity would be used for recovery and gait reeducation, may arise through the patients functional ability.

• Biomolecules & Therapeutics
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• 제27권5호
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• pp.442-449
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• 2019

This study sought to evaluate the effects of Asiatic acid in LPS-induced BV2 microglia cells and 1-methyl-4-phenyl-pyridine ($MPP^+$)-induced SH-SY5Y cells, to investigate the potential anti-inflammatory mechanisms of Asiatic acid in Parkinson's disease (PD). SH-SY5Y cells were induced using $MPP^+$ to establish as an in vitro model of PD, so that the effects of Asiatic acid on dopaminergic neurons could be examined. The NLRP3 inflammasome was activated in BV2 microglia cells to explore potential mechanisms for the neuroprotective effects of Asiatic acid. We showed that Asiatic acid reduced intracellular production of mitochondrial reactive oxygen species and altered the mitochondrial membrane potential to regulate mitochondrial dysfunction, and suppressed the NLRP3 inflammasome in microglia cells. We additionally found that treatment with Asiatic acid directly improved SH-SY5Y cell viability and mitochondrial dysfunction induced by $MPP^+$. These data demonstrate that Asiatic acid both inhibits the activation of the NLRP3 inflammasome by downregulating mitochondrial reactive oxygen species directly to protect dopaminergic neurons from, and improves mitochondrial dysfunction in SH-SY5Y cells, which were established as a model of Parkinson's disease. Our finding reveals that Asiatic acid protects dopaminergic neurons from neuroinflammation by suppressing NLRP3 inflammasome activation in microglia cells as well as protecting dopaminergic neurons directly. This suggests a promising clinical use of Asiatic acid for PD therapy.

• 인간행동과 음악연구
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• 제20권2호
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• pp.33-60
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• 2023

본 연구는 국외 파킨슨병 환자의 신체 재활을 위해 음악을 사용한 중재 연구의 연구 특성을 분석 및 고찰한 연구로 최근 20년간 진행된 연구 중 24편의 중재연구를 음악사용 수준에 따라 분류하여 요약 제시하였다. 분석된 연구 내용을 통해 파킨슨병 환자의 운동 산출 시 움직임의 시작 및 종료와 관련된 타이밍 문제를 개선할 수 있는 음악 요소가 무엇인지에 대해 고찰하였다. 분석 결과, 신체 기능의 변화를 유도하기 위해 제공한 음악사용 수준의 차이에 따라 음악 기반 중재연구(music-based intervention) 6편과 리듬기반 중재연구(rhythm-based intervention) 18편으로 나타났다. 이처럼 음악 수준에 따른 연구 특성을 고찰 후 음악사용의 공통 요소인 '리듬'이 대상자의 문제 개선에 적합한 중재 요소였음을 결론 도출하였다. 또한 연구자의 특성이 음악 요소의 활용 범위 및 음악사용의 정도와 관련이 있으며, 이것이 중재 효과의 다양성과 관련이 있다고 제시하였다. 따라서 본 연구는 실제 임상 환경에서 파킨슨병 환자를 포함하여 다양한 신체기능 문제 개선을 위한 신체 재활 중재에 적용이 가능한 음악사용의 근거를 학술적으로 제시하는 것으로 사료된다.

• Genomics & Informatics
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• 제19권1호
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• pp.7.1-7.13
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• 2021

Levodopa (L-DOPA) therapy is normally practised to treat motor pattern associated with Parkinson disease (PD). Additionally, several inhibitory drugs such as Entacapone and Opicapone are also cosupplemented to protect peripheral inactivation of exogenous L-DOPA (~80%) that occurs due to metabolic activity of the enzyme catechol-O-methyltransferase (COMT). Although, both Entacapone and Opicapone have U.S. Food and Drug Administration approval but regular use of these drugs is associated with high risk of side effects. Thus, authors have focused on in silico discovery of phytochemicals and evaluation of their effectiveness against human soluble COMT using virtual screening, molecular docking, drug-like property prediction, generation of pharmacophoric property, and molecular dynamics simulation. Overall, study proposed, nine phytochemicals (withaphysalin D, withaphysalin N, withaferin A, withacnistin, withaphysalin C, withaphysalin O, withanolide B, withasomnine, and withaphysalin F) of plant Withania somnifera have strong binding efficiency against human COMT in comparison to both of the drugs i.e., Opicapone and Entacapone, thus may be used as putative bioenhancer in L-DOPA therapy. The present study needs further experimental validation to be used as an adjuvant in PD treatment.

• KSBB Journal
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• 제20권4호
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• pp.323-327
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• 2005

조직을 이용한 역전사 (RT)-PCR법을 이용하면 원하는 특정유전자의 발현을 비교적 정확하게 알 수 있지만 조직의 RNA를 이용하므로 세포단위의 정확한 유전자 발현을 알기에는 한계가 있다. 특히 그 기능과 성질이 다른 세포가 무수하게 많이 혼재하는 두뇌와 같은 조직은 신경계의 각종 뉴런(신경세포), 글리어 (glial cell) 등이 서로 얽혀 있다. 대표적인 신경세포의 degeneration 질병으로는 파킨슨병 (Parkinson's disease; PD)이 있다. 파킨슨병은 사람의 신경세포 관련 질병에 있어서 가장 일반적인 질병의 하나이다. PD의 가장 중요한 원인은 도파민 생성 신경세포의 퇴행 혹은 사멸에 기인하여 도파민 (dopamine)이라는 신경전달물질이 감소하는 것이 그 원인이다. 도파민과 같은 카테콜아민의 생합성에 관련된 효소는 타이로신 하이드록실레이스 (TH), 도파 데카르복실레이스 (DDC) 등이 알려져 있다. 그러나 그런 효소들의 생화학적 연구는 많이 되어 있음에도 불구하고 단일 흑질 신경세포에서의 이들 관련 유전자의 발현 양상에 대해서는 알려진 바가 거의 없다. PD와 관련된 유전자의 발현 정도를 밝히기 위하여, 레이저 다이섹터 (laser micro-dissector)에 의한 단일 신경세포의 분리에 착수하였다. 정해진 방법에 따라 정상 대조구 (비PD)와 PD 환자에서 각각 한 개 또는 여러 개를 성공적으로 분리한 흑질 신경세포를 이용하여 유전자 특이적 프라이머를 사용하여 RT-PCR을 행하였다. 그 결과, 단 한 개의 신경세포에서도 여러 개의 세포를 사용한 것과 같은 동일한 결과를 얻는 데 성공하였다. PD환자의 뇌에서 분리한 10개의 독립적인 세포의 예에서는 각 세포간의 발현차이가 인정되었으며, 특히 TH 유전자의 발현은 상당히 높은 확률로 검출되지 않았다. 이 결과로 단일 신경세포에서의 mRNA양을 검출하기 위해서는 본 본문의 RT-PCR법이 효과적인 방법임을 알 수 있다.

• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.299-306
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• 2013

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely used as a treatment for the movement disturbances caused by Parkinson's disease (PD). Despite successful application of DBS, its mechanism of therapeutic effect is not clearly understood. Because PD results from the degeneration of dopamine neurons that affect the basal ganglia (BG) network, investigation of neuronal responses of BG neurons during STN DBS can provide informative insights for the understanding of the mechanism of therapeutic effect. However, it is difficult to observe neuronal activity during DBS because of large stimulation artifacts. Here, we report the observation of neuronal activities of the globus pallidus (GP) in normal and PD model rats during electrical stimulation of the STN. A custom artifact removal technique was devised to enable monitoring of neural activity during stimulation. We investigated how GP neurons responded to STN stimulation at various stimulation frequencies (10, 50, 90 and 130 Hz). It was observed that activities of GP neurons were modulated by stimulation frequency of the STN and significantly inhibited by high frequency stimulation above 50 Hz. These findings suggest that GP neuronal activity is effectively modulated by STN stimulation and strongly dependent on the frequency of stimulation.

• 약학회지
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• 제59권3호
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• pp.127-134
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• 2015

The aim of this study was to investigate the correlation among age, symptoms and initial medication (IM), and the tolerance duration of IM in Korean people with Parkinson's disease (PD). We studied 60 patients with untreated early PD who were initially diagnosed in our hospital between Jun 2006 and Sep 2014. We collected data on sex, age at diagnosis, symptom duration until diagnosis, main motor symptoms, frequency and duration of IM through electronic medical records. We divided patients into groups depending on the number of drugs (MONO/COMBI) and whether to contain dopaminergic property (DOPA/NDOPA). We analyzed the correlation between age and symptoms in each two groups and calculated the mean tolerance duration of IM in each of the groups. The mean symptom duration until diagnosis was 12.2 months. The most frequent drug was levodopa formulations (80%) compared to dopamine agonists (58.3%). The number of patients in the COMBI group (63.3%) was more than that in the MONO group (36.7%). Half of the patients in the COMBI group were taking LDF+DA (50%). Except for tremor, no other symptom showed a significant correlation between with IM. The mean tolerance duration of IM was within 200 days. The mean duration for COMBI group (342.7 days) was longer than that for MONO group (209.8 days). Among regimens, the mean tolerance duration of DOPA group (293.3 days) was longer than for NDOPA group (251.4 days). There was no difference in survival curves between any of the two groups. We found that patients experienced symptoms for over a year in Korea. This indicates that diagnosis time is faster than reported in other previous studies. The longest tolerance duration among IM was for dopaminergic combination therapy. More research is needed to design the most appropriate treatment for PD in Korean patients.

• BMB Reports
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• 제46권9호
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• pp.454-459
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• 2013

LRRK2 (leucine-rich repeat kinase 2) has been identified as a gene corresponding to PARK8, an autosomal-dominant gene for familial Parkinson's disease (PD). LRRK2 pathogenic-specific mutants induce neurotoxicity and shorten neurites. To elucidate the mechanism underlying LRRK2 expression, we constructed the LRRK2-promoter-luciferase reporter and used it for promoter analysis. We found that the glucocorticoid receptor (GR) transactivated LRRK2 in a ligand-dependent manner. Using quantitative RT-PCR and Western analysis, we further showed that treatment with dexamethasone, a synthetic GR ligand, induced LRRK2 expression at both the transcriptional and translational levels, in dopaminergic MN9D cells. Dexamethasone treatment also increased expression of ${\alpha}$-synuclein, another PD causative gene, and enhanced transactivation of the ${\alpha}$-synuclein promoter-luciferase reporter. In addition, dexamethasone treatment to MN9D cells weakly induced cytotoxicity based on an LDH assay. Because glucocorticoid hormones are secreted in response to stress, our data suggest that stress might be a related factor in the pathogenesis of PD.

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.118-125
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• 2011

Free radical scavenging and antioxidants have attracted attention as a way to prevent the progression of Parkinson's disease (PD). This study was carried out to investigate the effects of n-hexane fraction from Laurus nobilis L. (Lauraceae) leaves (HFL) on dopamine (DA)-induced intracellular reactive oxygen species (ROS) production and apoptosis in human neuroblastoma SH-SY5Y cells. Compared with apomorphine (APO, $IC_{50}=18.1\;{\mu}M$) as a positive control, the HFL $IC_{50}$ value for DA-induced apoptosis was $3.0\;{\mu}g/ml$, and two major compounds from HFL, costunolide and dehydrocostus lactone, were $7.3\;{\mu}M$ and $3.6\;{\mu}M$, respectively. HFL and these major compounds significantly inhibited ROS generation in DA-induced SH-SY5Y cells. A rodent 6-hydroxydopamine (6-OHDA) model of PD was employed to investigate the potential neuroprotective effects of HFL in vivo. 6-OHDA was injected into the substantia nigra of young adult rats and an immunohistochemical analysis was conducted to quantitate the tyrosine hydroxylase (TH)-positive neurons. HFL significantly inhibited 6-OHDA-induced TH-positive cell loss in the substantia nigra and also reduced DA induced $\alpha$-synuclein (SYN) formation in SH-SY5Y cells. These results indicate that HFL may have neuroprotective effects against DA-induced in vitro and in vivo models of PD.