• Journal of Environmental Science International
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• v.32 no.10
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• pp.723-729
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• 2023

Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by dopaminergic neuronal loss in the substantia nigra, resulting in reduced dopamine levels and consequent motor dysfunction. Genetic and environmental factors contribute to oxidative stress in PD. Cicadidae Periostracum (CP), a traditional Korean medicine, has shown neuroprotective effects against MPTP-induced neurotoxicity in PD. However, its effects on the 6-hydroxydopamine (6-OHDA) model have not been established. This study examined CP's effects on a 6-OHDA-induced PD model. CP protected against 6-OHDA damage in both in vitro and in vivo studies. Furthermore, CP reduced the production of reactive oxygen species, inhibited apoptosis, preserved dopamine levels, protected tyrosine hydroxylase in the substantia nigra, and improved motor function. These findings suggest that CP may delay PD progression by maintaining the redox balance.

• BMB Reports
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• v.52 no.4
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• pp.250-258
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• 2019

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by selective and progressive loss of dopaminergic neurons. Genetic and environmental risk factors are associated with this disease. The genetic factors are composed of approximately 20 genes, such as SNCA, parkin, PTEN-induced kinase1 (pink1), leucine-rich repeat kinase 2 (LRRK2), ATP13A2, MAPT, VPS35, and DJ-1, whereas the environmental factors consist of oxidative stress-induced toxins such as 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), rotenone, and paraquat. The analyses of their functions and mechanisms have provided important insights into the disease process, which has demonstrated that these factors cause oxidative damage and mitochondrial dysfunction. The most invaluable studies have been performed using disease model organisms, such as mice, fruit flies, and worms. Among them, Drosophila melanogaster has emerged as an excellent model organism to study both environmental and genetic factors and provide insights to the pathways relevant for PD pathogenesis, facilitating development of therapeutic strategies. In this review, we have focused on the fly model organism to summarize recent progress, including pathogenesis, neuroprotective compounds, and newer approaches.

• BMB Reports
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• v.43 no.4
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• pp.225-232
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• 2010

Parkinson's Disease (PD) is a common neurodegenerative disease characterized by the progressive degeneration of nigrostriatal dopaminergic (DA) neurons. Although the causative factors of PD remain elusive, many studies on PD animal models or humans suggest that glial activation along with neuroinflammatory processes contribute to the initiation or progression of PD. Additionally, several groups have proposed that dysfunction of the blood-brain barrier (BBB) combined with infiltration of peripheral immune cells play important roles in the degeneration of DA neurons. However, these neuroinflammatory events have only been investigated separately, and the issue of whether these phenomena are neuroprotective or neurotoxic remains controversial. We here review the current knowledge regarding the functions of these neuroinflammatory processes in the brain. Finally, we describe therapeutic strategies for the regulation of neuroinflammation with the goal of improving the symptoms of PD.

• Nutritional Sciences
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• v.9 no.2
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• pp.61-67
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• 2006

Green tea has attracted attention with respect to its potential for preventing and treating neurodegenerative disease. The neurotoxin, 6-hydroxydopamine (6-OHDA), was used to produce experimental Parkinson's disease (PD) model. The purpose of this study was to investigate the effects of green tea diet on behavioral changes, striatal dopamine content, and hepatic antioxidant parameters of PD model rats. In this study, we used male Sprague-Dawley rats weighing $200\sim220g$ and injected 6-OHDA into the right substantia nigra and medial forebrain bundle of the brain. The supply of green tea diet was started at 2 weeks before 6-OHDA lesion and continually supplied during 0, 2, and 4 weeks after 6-OHDA lesion (GT-0, GT-2, GT-4). Behavioral disturbance was measured by the stepping and d-amphetamine drug-induced rotation tests. Then, we assayed the striatal dopamine content and the hepatic malondialdehyde (MDA), hydrogen peroxide $(H_2O_2)$, and superoxide dismutase (SOD) activity. The percentage of lesioned forepaw to non-lesioned forepaw step scores was the highest in GT-4 group among all groups at both 3 and 4 weeks after 6-OHDA lesion. At 4 weeks after 6-OHDA lesion, the rotation score was the lowest in GT-2 group (p<0.05). However, increasing rate of the rotation score from 2 to 4 weeks after 6-OHDA lesion was the lowest in GT-4 group. The striatal dopamine content was not significantly different among four groups by green tea diet. The hepatic MDA level was the lowest in GT-4 group among four groups. The hepatic SOD activity was increased with the prolongation of green tea diet period These results suggest that green tea diet affects behavioral changes in rats of PD model. It seems that continuous green tea supplementation has an influence on the reduction of behavioral disturbance and the hepatic MDA level. Accordingly, continuous green tea supplementation was recommended for the prevention and treatment of PD. However, further studies are needed to investigate the mechanisms and efficacy of green tea in PD.

• Korean Journal of Biological Psychiatry
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• v.24 no.1
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• pp.19-25
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• 2017

Previous studies have found that firefighters have a tenfold higher prevalence of Parkinson's disease (PD) compare to the general population. Firefighters are constantly exposed to various occupational hazards including toxic chemicals of fire residue and the toxic chemicals can effects development and progression of PD. Nevertheless, there were no studies about the association between exposure to chemical byproducts of combustion and the development of PD among firefighters. Thus the aim of this study is to look into existing researches regarding the effect of chemical byproducts of combustion on the development of PD. An extensive literature search was conducted to identify harmful chemical components of smoke and fire residue, using the PubMed database during November of 2016. We searched for relevant articles by combining several keywords that contained "Parkinson's disease" and each of the different toxic chemicals, yielding a total of 1401 articles. After applying the selection criteria, 12 articles were chosen. Chemical substances reported to have a harmful effect on PD, in at least one article, were carbon monoxide, toluene, manganese and lead. Carbon monoxide and metal substances including manganese and lead were found to be associated with an increased PD risk in more than two articles. There was a heightened risk of PD in firefighters due to exposure of chemical byproducts of combustion including carbon monoxide, toluene, manganese and lead. However, to the best of our knowledge, to support this result we need more systematic epidemiological studies about these risk factors of PD among firefighters. In addition, further studies for the effects of prolonged exposure to toxic fire residue on the development and progression of PD in firefighters are needed.

• Journal of Korean Neurosurgical Society
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• v.67 no.5
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• pp.510-520
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• 2024

Objective : Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The treatment of PD aims to alleviate motor symptoms by replacing the reduced endogenous dopamine. Currently, there are no disease-modifying agents for the treatment of PD. Zebrafish (Danio rerio) have emerged as an effective tool for new drug discovery and screening in the age of translational research. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause a similar loss of dopaminergic neurons in the human midbrain, with corresponding Parkinsonian symptoms. L-type calcium channels (LTCCs) have been implicated in the generation of mitochondrial oxidative stress, which underlies the pathogenesis of PD. Therefore, we investigated the neuro-restorative effect of LTCC inhibition in an MPTP-induced zebrafish PD model and suggested a possible drug candidate that might modify the progression of PD. Methods : All experiments were conducted using a line of transgenic zebrafish, Tg(dat:EGFP), in which green fluorescent protein (GFP) is expressed in dopaminergic neurons. The experimental groups were exposed to 500 μmol MPTP from 1 to 3 days post fertilization (dpf). The drug candidates : levodopa 1 mmol, nifedipine 10 μmol, nimodipine 3.5 μmol, diethylstilbestrol 0.3 μmol, luteolin 100 μmol, and calcitriol 0.25 μmol were exposed from 3 to 5 dpf. Locomotor activity was assessed by automated tracking and dopaminergic neurons were visualized in vivo by confocal microscopy. Results : Levodopa, nimodipine, diethylstilbestrol, and calcitriol had significant positive effects on the restoration of motor behavior, which was damaged by MPTP. Nimodipine and calcitriol have significant positive effects on the restoration of dopaminergic neurons, which were reduced by MPTP. Through locomotor analysis and dopaminergic neuron quantification, we identified the neuro-restorative effects of nimodipine and calcitriol in zebrafish MPTP-induced PD model. Conclusion : The present study identified the neuro-restorative effects of nimodipine and calcitriol in an MPTP-induced zebrafish model of PD. They restored dopaminergic neurons which were damaged due to the effects of MPTP and normalized the locomotor activity. LTCCs have potential pathological roles in neurodevelopmental and neurodegenerative disorders. Zebrafish are highly amenable to high-throughput drug screening and might, therefore, be a useful tool to work towards the identification of disease-modifying treatment for PD. Further studies including zebrafish genetic models to elucidate the mechanism of action of the disease-modifying candidate by investigating Ca2+ influx and mitochondrial function in dopaminergic neurons, are needed to reveal the pathogenesis of PD and develop disease-modifying treatments for PD.

• Korean Journal of Clinical Pharmacy
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• v.23 no.1
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• pp.33-41
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• 2013

Background: Prevalence of depression comorbid with neurologic disorders such as Alzheimer' disease (AD), Parkinson's disease (PD) and vascular dementia (VD) is higher than that of primary depression. Antidepressant medications, suggested by many researches for depression comorbid with neurologic disorders such as AD, PD and VD, are mainly selective serotonin reuptake inhibitors (SSRI). Objective: The primary objective of this study is the evaluation of antidepressant drug therapy for AD, PD and VD. Method: This study was a retrospective study based on medical records, carried out for 3 years and 6 months (Jan. 2007~Jul. 2010). Patients, diagnosed as comorbid depression through Beck Depression Inventory (BDI), Cornell Depression Scale (CDS), Geriatric Depression Scale (GDS) among neurologic out-patients of Chungnam National University Hospital because of AD, PD and VD, were selected. The results were evaluated by efficacy and safety of antidepressant drug therapy. Results: In result, the prescribing rates of antidepressants were 30%, 55% and 40% for each AD, PD and VD. Depression cure rates of patients receiving antidepressants vs patients not receiving antidepressants were 40% vs 39%, 33% vs 23% and 38% vs 30% for AD, PD and VD. The frequencies of prescriptoin of SSRI were 21%, 11% and 27% for each AD, PD and VD. The frequencies of prescriptoin of benzodiazepine (BZD) was 61%, 82% and 61% for each AD, PD and VD. The ratio of single BZD prescription was more than that of combination prescription of antidepressants. Tricyclic antidepressants (TCA) were rarely prescribed. The rate of patients with BZD-related side effects was 54%. The most frequent side effects of BZD were dizziness (30%), drowsiness (21%) and headache (16%). Side effects of SSRI were rare. Conclusion: In conclusion, the frequencies of prescription of antidepressants were not common for AD, PD and VD. There was little difference in depression cure rate between patient receiving antidepressants and not receiving. Even though SSRI has to be the highest priority of usage, the frequencies of prescription of SSRI were lower than those of BZD. Additional researches and efforts are required to improve antidepressant drug therapy for neurologic disorders such as AD, PD and VD.

• Korean Journal of Applied Biomechanics
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• v.26 no.3
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• pp.293-301
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• 2016

Objective: The purpose of this study was to analyze the effects of freezing of gait and visual information on the static postural control ability in patients with Parkinson's Disease (PD) during the bipedal stance with feet together. Method: This study included a total of 36 patients with PD; the freezer group included 17 PD patients (age: $69.3{\pm}6.2yrs$, height: $159.6{\pm}9.0cm$, weight: $63.4{\pm}9.78kg$) and the nonfreezer group included 19 PD patients (age: $71.4{\pm}5.6yrs$, height: $155.8{\pm}7.1cm$, weight: $57.7{\pm}8.6kg$). Static postural control ability was analyzed using variables of center of pressure (COP) and dividing by mediolateral, anteroposterior, and integration factors during a bipedal stance with the eyes open and closed. Results: Freezers and nonfreezers showed increases in anteroposterior velocity, mediolateral velocity, averaged velocity, and mediolateral 95% edge frequency when visual information was blocked. Additionally, freezers had greater anteroposterior range, 95% confidence ellipse area, and COP anteroposterior mean position than nonfreezers. Conclusion: Freezers and nonfreezers showed a reduction in static postural control ability when visual information was blocked. Additionally, the results of this study found a significant difference in static postural control ability between freezers and nonfreezers with PD. In particular, anteroposterior range, 95% confidence ellipse area, and COP anteroposterior mean position might be used to distinguish between freezers and nonfreezers with PD.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.615-629
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• 2021

An active compound, triterpene saponin, astersaponin I (AKNS-2) was isolated from Aster koraiensis Nakai (AKNS) and the autophagy activation and neuroprotective effect was investigated on in vitro and in vivo Parkinson's disease (PD) models. The autophagy-regulating effect of AKNS-2 was monitored by analyzing the expression of autophagy-related protein markers in SH-SY5Y cells using Western blot and fluorescent protein quenching assays. The neuroprotection of AKNS-2 was tested by using a 1-methyl-4-phenyl-2,3-dihydropyridium ion (MPP⁺)-induced in vitro PD model in SH-SY5Y cells and an MPTP-induced in vivo PD model in mice. The compound-treated SH-SY5Y cells not only showed enhanced microtubule-associated protein 1A/1B-light chain 3-II (LC3-II) and decreased sequestosome 1 (p62) expression but also showed increased phosphorylated extracellular signal-regulated kinases (p-Erk), phosphorylated AMP-activated protein kinase (p-AMPK) and phosphorylated unc-51-like kinase (p-ULK) and decreased phosphorylated mammalian target of rapamycin (p-mTOR) expression. AKNS-2-activated autophagy could be inhibited by the Erk inhibitor U0126 and by AMPK siRNA. In the MPP⁺-induced in vitro PD model, AKNS-2 reversed the reduced cell viability and tyrosine hydroxylase (TH) levels and reduced the induced α-synuclein level. In an MPTP-induced in vivo PD model, AKNS-2 improved mice behavioral performance, and it restored dopamine synthesis and TH and α-synuclein expression in mouse brain tissues. Consistently, AKNS-2 also modulated the expressions of autophagy related markers in mouse brain tissue. Thus, AKNS-2 upregulates autophagy by activating the Erk/mTOR and AMPK/mTOR pathways. AKNS-2 exerts its neuroprotective effect through autophagy activation and may serve as a potential candidate for PD therapy.

• Korean Journal of Clinical Pharmacy
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• v.28 no.4
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• pp.285-292
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• 2018

Background: Long-term levodopa therapy relieves the motor dysfunction associated with Parkinson's disease (PD), but has various effects on non-motor symptoms, including cognitive dysfunction, hallucinations, and affective disorders, and can exacerbate certain aspects of dementia-like cognitive dysfunction. Here, we investigated the relationship between levodopa treatment and development of dementia in patients with PD. Methods: This retrospective study analyzed 76 consecutive patients with PD who had taken levodopa between 2011 and 2015. The participants were initially free of dementia and had initial daily levodopa doses of below 600 mg. Patients who did and did not develop comorbid dementia were compared in terms of potential predictor variables, including PD onset age, sex, levodopa doses, and non-dementia comorbidities. Results: Of the 76 patients, 21 (27.6%) developed dementia, which was followed by hallucinations and insomnia. The independent predictors of incident dementia were PD onset age and second-year and third-year average levodopa doses that were higher than the first-year average levodopa dose. Patients who developed dementia had significantly higher average daily levodopa doses and levodopa dose increases over the 6-year treatment period than those who did not develop dementia. In addition, patients with higher levodopa doses were more likely to experience hallucinations. Conclusion: These results suggest that increases in levodopa doses may be associated with a greater risk of cognitive impairment in patients with PD. Therefore, motor and cognitive functions and levodopa dose increases should be evaluated regularly during long-term levodopa therapy in patients with PD.