• Title/Summary/Keyword: s Disease(PD)

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Abrogation of the Circadian Nuclear Receptor REV-ERBα Exacerbates 6-Hydroxydopamine-Induced Dopaminergic Neurodegeneration

  • Kim, Jeongah;Jang, Sangwon;Choi, Mijung;Chung, Sooyoung;Choe, Youngshik;Choe, Han Kyoung;Son, Gi Hoon;Rhee, Kunsoo;Kim, Kyungjin
    • Molecules and Cells
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    • v.41 no.8
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    • pp.742-752
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    • 2018
  • Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive degeneration of dopaminergic (DAergic) neurons, particularly in the substantia nigra (SN). Although circadian dysfunction has been suggested as one of the pathophysiological risk factors for PD, the exact molecular link between the circadian clock and PD remains largely unclear. We have recently demonstrated that $REV-ERB{\alpha}$, a circadian nuclear receptor, serves as a key molecular link between the circadian and DAergic systems. It competitively cooperates with NURR1, another nuclear receptor required for the optimal development and function of DA neurons, to control DAergic gene transcription. Considering our previous findings, we hypothesize that $REV-ERB{\alpha}$ may have a role in the onset and/or progression of PD. In the present study, we therefore aimed to elucidate whether genetic abrogation of $REV-ERB{\alpha}$ affects PD-related phenotypes in a mouse model of PD produced by a unilateral injection of 6-hydroxydopamine (6-OHDA) into the dorsal striatum. $REV-ERB{\alpha}$ deficiency significantly exacerbated 6-OHDA-induced motor deficits as well as DAergic neuronal loss in the vertebral midbrain including the SN and the ventral tegmental area. The exacerbated DAergic degeneration likely involves neuroinflammation-mediated neurotoxicity. The $REV-erb{\alpha}$ knockout mice showed prolonged microglial activation in the SN along with the over-production of interleukin $1{\beta}$, a pro-inflammatory cytokine, in response to 6-OHDA. In conclusion, the present study demonstrates for the first time that genetic abrogation of $REV-ERB{\alpha}$ can increase vulnerability of DAergic neurons to neurotoxic insults, such as 6-OHDA, thereby implying that its normal function may be beneficial for maintaining DAergic neuron populations during PD progression.

In Vivo $^1H$ MR Spectroscopic Study on Levodopa-Treated Parkison's Disease

  • Choe, Bo-Young;Baik, Hyun-Man;Son, Byung-Chul;Kim, Moon-Chan;Kim, Euy-Neyung;Suh, Tae-Suk;Lee, Hyoung-Koo;Shinn, Kyung-Sub
    • Journal of the Korean Magnetic Resonance Society
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    • v.4 no.1
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    • pp.19-28
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    • 2000
  • Authors evaluated alterations of observable metabolite ratios between the cerebral lesion and the contralateral region related to the clinical symptomatic side in levodopa-treated Parkinson's disease (PD) and investigated correlation between age in patients with PD and metabolite ratios of the lesion. Patients with levodopa-treated PD (n = 54) and age-matched normal controls (n = 15) underwent magnetic resonance spectroscopy (MRS) examinations using a stimulated echo acquisition mode (STEAM) pulse sequence that provided 2$\times$2$\times$2 cm3 volume of interest in the selected regions of substantia nigra (SN) and putamed-globus pallidus (PG). To evaluate dependence of metabolite ratios on age, we divided into two groups (i.e., younger and older age). We quantitatively measured N-acetylaspartate (NAA), creatine (Cr), choline-containing compounds (Cho), inositols (Ins), and the sum of glutamate (Glx) and GABA levels and obtained proton metabolite ratios relative to Cr using a Marquart algorithm. Compared with the contralateral region, a significant neuronal laterality of the NAA/Cr ratio in the lesion of SN related to the clinical symptomatic side was established (P = 0.01), but was not established in the lesion of PG (P = 0.24). Also, Cho/Cr ratio tended toward significance in the lesion of SN (P = 0.07) and was statistically significant in the lesion of PG(P = 0.01). Compared with that in the younger age group, NAA/Cr ratio in the older age was decreased in the lesion of SN (P = 0.02), while NAA/Cr ratio was not statistically significant in the lesion of PG ( P = 0.21). Significant metabolic alterations of NAA/Cr and Cho/Cr ratios might be closely related with functional changes of neuropathological process in SN and PG of levodopa treated PD and could be a valuable finding for evaluation of the PD. A trend of NAA/Cr reduction, being statistically significant in older patients, could be indicative of more pronounced neuronal damage in the SN of the progressive PD.

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Oxidative Modification of Neurofilament-L by the Cytochrome c and Hydrogen Peroxide System

  • Kang, Jung-Hoon
    • Bulletin of the Korean Chemical Society
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    • v.28 no.1
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    • pp.77-80
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    • 2007
  • As neurofilament proteins are major cytoskeletal components of neuron, abnormality of neurofilament is proposed in brain with neurodegenerative disorders such as Parkinson's disease (PD). Since oxidative stress might play a critical role in altering normal brain proteins, we investigated the oxidative modification of neurofilament-L (NF-L) induced by the reaction of cytochrome c with H2O2. When NF-L was incubated with cytochrome c and H2O2, the protein aggregation was increased in cytochrome c and H2O2 concentrationsdependent manner. Radical scavengers, azide, formate and N-acetyl cysteine, prevented the aggregation of NFL induced by the cytochrome c/H2O2 system. The formations of carbonyl group and dityrosine were obtained in cytochrome c/H2O2-mediated NF-L aggregates. Iron specific chelator, desferoxamine, prevented the cytochrome c/H2O2 system-mediated NF-L aggregation. These results suggest that the cytochrome c/H2O2 system may be related to abnormal aggregation of NF-L which may be involved in the pathogenesis of PD and related disorders.

A Biomechanical Gait Analysis of Patients with Parkinson's Disease by Auditory Cues Velocity (청각 신호 속도에 따른 파킨슨병 환자의 생역학적 보행 분석)

  • Kim, Eun-Jung;Han, Jin-Tae;Jung, Jae-Min
    • Journal of the Korean Society of Physical Medicine
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    • v.8 no.1
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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.

Factors Influencing Self Care Performance in Patients with Parkinson's Disease (파킨슨병 환자의 자가간호수행에 영향을 미치는 요인)

  • Kim, Yu-Ri;Min, Hye-Sook
    • The Korean Journal of Rehabilitation Nursing
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    • v.13 no.2
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    • pp.140-150
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    • 2010
  • Purpose: This study aims to find the factors that affect the degree of self-care performance in Parkinson's disease (PD) patients. Method: This study used a descriptive correlational design. The data were collected using a sample of 80 PD patients, from the university affiliated Parkinson Center in Busan. Pearson's correlations and multiple regression analyses were conducted using the SPSS 18.0. Results: The mean score of the self-care performance was 3.61 (${\pm}0.40$). The highest score observed of self-care performance subscale was medication subscale ($4.55{\pm}0.50$) and the lowest score was observed in the exercise subscale ($3.03{\pm}0.64$). The self-care performance had significant correlations with depression (r=-.32, p<.01), self-care knowledge (r=.28, p<.05), function of motion (r=.25, p<.05), ability of daily activity (r=.22, p<.05), self-efficacy (r=.24, p<.05), and support from medical staff (r=.24, p<.05). The significant predictors of self-care performance included depression (${\beta}=-.28$), status of employment (${\beta}=-.27$), self-care knowledge (${\beta}=-.21$), support from medical staff (${\beta}=-.28$), and educational level (${\beta}=-.28$), accounting for 34% of the variance in the self-care performance. Conclusion: Depression, self-care knowledge, medical support are significant predictors which affect the self-care performance with PD patients.

Asiatic Acid Protects Dopaminergic Neurons from Neuroinflammation by Suppressing Mitochondrial ROS Production

  • Chen, Dong;Zhang, Xiao-Ya;Sun, Jing;Cong, Qi-Jie;Chen, Wei-Xiong;Ahsan, Hafiz Muhammad;Gao, Jing;Qian, Jin-Jun
    • Biomolecules & Therapeutics
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    • v.27 no.5
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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.

A Review of Interventions Using Music for Physical Rehabilitation in Patients With Parkinson's Disease (국외 파킨슨병 환자 대상 음악을 활용한 신체재활 중재연구 고찰)

  • Kwon, Ha Young
    • Journal of Music and Human Behavior
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    • v.20 no.2
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    • pp.33-60
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    • 2023
  • This study is an analysis and review of the international research on interventions using music for the rehabilitation of patients with Parkinson's disease(PD). It categorizes 24 intervention studies conducted over the last 20 years based on the level of music usage and type of music utilized. The aim of this analysis was to identify which musical elements improved timing issues related to the initiation and cessation of movement in patients with PD. The studies involved six with music-based interventions and 18 with rhythm-based interventions, depending on the level of music usage. Rhythm, a common element in music, was a suitable factor for addressing the participants' issues. Furthermore, this review suggests that the characteristics of the researchers impact the extent to which musical elements are used and the diversity of those elements, which influences the intervention's effectiveness. Therefore, this study provides information on how to specify and systematically consider intervention efforts and the use of musical elements that can be applied in rehabilitation for patients with PD.

Protective effects of PEP-1-Catalase on stress-induced cellular toxicity and MPTP-induced Parkinson's disease

  • Eom, Seon Ae;Kim, Dae Won;Shin, Min Jea;Ahn, Eun Hee;Chung, Seok Young;Sohn, Eun Jeong;Jo, Hyo Sang;Jeon, Su-Jeong;Kim, Duk-Soo;Kwon, Hyeok Yil;Cho, Sung-Woo;Han, Kyu Hyung;Park, Jinseu;Eum, Won Sik;Choi, Soo Young
    • BMB Reports
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    • v.48 no.7
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    • pp.395-400
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    • 2015
  • Parkinson's disease (PD) is a neurodegenerative disability caused by a decrease of dopaminergic neurons in the substantia nigra (SN). Although the etiology of PD is not clear, oxidative stress is believed to lead to PD. Catalase is antioxidant enzyme which plays an active role in cells as a reactive oxygen species (ROS) scavenger. Thus, we investigated whether PEP-1-Catalase protects against 1-methyl-4-phenylpyridinium (MPP+) induced SH-SY5Y neuronal cell death and in a 1-methyl-4-phenyl-1,2,3,6-trtrahydropyridine (MPTP) induced PD animal model. PEP-1-Catalase transduced into SH-SY5Y cells significantly protecting them against MPP+-induced death by decreasing ROS and regulating cellular survival signals including Akt, Bax, Bcl-2, and p38. Immunohistochemical analysis showed that transduced PEP-1-Catalase markedly protected against neuronal cell death in the SN in the PD animal model. Our results indicate that PEP-1-Catalase may have potential as a therapeutic agent for PD and other oxidative stress related diseases. [BMB Reports 2015; 48(7): 395-400]

The Effects of Tai Chi Exercise on Depression, Quality of Life and Self-efficacy in Patients with Parkinson's Disease (태극권이 파킨슨병 환자의 우울, 자기효능감 및 삶의 질에 미치는 효과)

  • Choi, Dong-Won;Sohng, Kyeong-Yae
    • Journal of Korean Academy of Fundamentals of Nursing
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    • v.15 no.4
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    • pp.467-474
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    • 2008
  • Purpose: To examine the effects of Tai Chi exercise (TCE) on depression, quality of life and self-efficacy in patients with Parkinson's disease (PD). Method: A nonequivalent control-group pre and posttest design was used. Of the 30 participants 15 were assigned to the experimental group and 15 to the control group. The experimental group participated in 8 weeks of TCE which included one day of exercise with instructor on site and 3 days of self-exercise at home guided by a videotape. Results: The 8 weeks of TCE were found to be significantly effective in enhancing quality of life and self-efficacy. However there was no significant difference in the level of depression. Conclusion: These results suggest that TCE has positive effect on quality of life and self-efficacy in patients with PD. Research over an extended period with the TCE intervention is recommended to identify further effects.

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Autophagy-enhancing and neuroprotective effects of Wonji-Gobon mixture (WGM) in a Parkinson's disease mouse model

  • Lee, Jin-Wook;Kwak, Jin-Young;Koh, Young-Mee;Ahn, Taek-Won
    • Journal of Applied Biological Chemistry
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    • v.61 no.4
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    • pp.341-349
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    • 2018
  • The aim of this study was to evaluate autophagy-enhancing and neuroprotective effects of Wonji-Gobon mixture (WGM), a traditional Chinese prescription medication, in Parkinson's disease (PD) mouse models. Our investigation found that WGM increased the expression of both Beclin1 and LC3b-II proteins as measured with western blot in the BV2 cell line; both proteins play a role in autophagy. WGM also increased the autophagy expression as measured by fluorescence-activated cell-sorting analysis in the BV2 cell line. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD models, WGM significantly increased the amount of dopamine in a striatum-substantia nigra suspension, produced notable results in the forced swim test, and increased serotonin as measured by high-performance liquid chromatography analysis; these results are indicative of neuroprotective effects. In summary, our findings indicate that WGM treatment has neuroprotective effects that are partially mediated by autophagy enhancement.