• Title/Summary/Keyword: Parkinson's disease model

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Pharmacokinetic and Pharmacodynamic Modeling of Levodopa in Parkinson Disease

  • Holford, Nick H.
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.220-222
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    • 2002
  • The concentration effect relationship (pharmacokinetic pharmacodynamic model, PKPD) of drugs used for Parkinson's disease is complex. The benefits and adverse effects of drug treatment have to be considered in terms of short term and long term effects. Acute effects, observed over hours and days, reflect symptomatic benefit while chronic effects, observed over months and years, also reveal influences on the progress of the disease. (omitted)

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Disease model organism for Parkinson disease: Drosophila melanogaster

  • Aryal, Binod;Lee, Youngseok
    • 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.

Improvements in Cognitive and Motor Function by a Nutrient Delivery System Containing Sialic Acid from Edible Bird's Nest (제비집 시알산 유래 영양전달체(Nutrient Delivery System)의 인지기능 및 운동기능 개선 효과)

  • Kim, Dong-Myong;Jung, Ju-Yeong;Lee, Hyung-Kon;Kwon, Yong-Seong;Baek, Jin-Hong;Han, In Suk
    • The Korean Journal of Food And Nutrition
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    • v.33 no.6
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    • pp.614-623
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    • 2020
  • The objective of this study was to produce a nutrient delivery system (NDS) using sialic acid extracted from edible bird's nest (EBN), which improves brain function in patients with Alzheimer's disease and Parkinson's disease, by affinity bead technology (ABT). The inhibitory activity of acetylcholinesterase (AChE) and pyramidal cells in the dentate gyrus of the hippocampus were analyzed to investigate the effect of a sialic acid NDS on Alzheimer's disease. Also, the effect of a sialic acid NDS on Parkinson's disease was evaluated by rota-rod test and pole test in an animal model. Among the groups treated with donepezil, EBN, and sialic acid NDS, the AChE activity was the lowest in the sialic acid NDS-treated group. The results of the hippocampus analysis of the rat model confirmed that the sialic acid NDS inhibited amyloid-beta accumulation depending upon the concentration. Also, the sialic acid NDS group showed more improvement in motor deterioration than the1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced group in both the rota-rod test and pole test. Therefore, the sialic acid NDS had an effect of protecting not only Alzheimer's disease by inhibiting AChE and amyloid-beta accumulation, but Parkinson's disease by preventing neurotoxicity induced by MPTP.

Rebound excitability mediates motor abnormalities in Parkinson's disease

  • Kim, Jeongjin;Kim, Daesoo
    • BMB Reports
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    • v.51 no.1
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    • pp.3-4
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    • 2018
  • Parkinson's disease (PD) is a debilitating disorder resulting from loss of dopamine neurons. In dopamine deficient state, the basal ganglia increases inhibitory synaptic outputs to the thalamus. This increased inhibition by the basal ganglia output is known to reduce firing rate of thalamic neurons that relay motor signals to the motor cortex. This 'rate model' suggests that the reduced excitability of thalamic neurons is the key for inducing motor abnormalities in PD patients. We reveal that in response to inhibition, thalamic neurons generate rebound firing at the end of inhibition. This rebound firing increases motor cortical activity and induces muscular responses that triggers Parkinsonian motor dysfunction. Genetic and optogenetic intervention of the rebound firing prevent motor dysfunction in a mouse model of PD. Our results suggest that inhibitory synaptic mechanism mediates motor dysfunction by generating rebound excitability in the thalamocortical pathway.

Patient-specific pluripotent stem cell-based Parkinson's disease models showing endogenous alpha-synuclein aggregation

  • Oh, Yohan
    • BMB Reports
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    • v.52 no.6
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    • pp.349-359
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    • 2019
  • After the first research declaring the generation of human induced pluripotent stem cells (hiPSCs) in 2007, several attempts have been made to model neurodegenerative disease in vitro during the past decade. Parkinson's disease (PD) is the second most common neurodegenerative disorder, which is mainly characterized by motor dysfunction. The formation of unique and filamentous inclusion bodies called Lewy bodies (LBs) is the hallmark of both PD and dementia with LBs. The key pathology in PD is generally considered to be the alpha-synuclein (${\alpha}$-syn) accumulation, although it is still controversial whether this protein aggregation is a cause or consequence of neurodegeneration. In the present work, the recently published researches which recapitulated the ${\alpha}$-syn aggregation phenomena in sporadic and familial PD hiPSC models were reviewed. Furthermore, the advantages and potentials of using patient-derived PD hiPSC with focus on ${\alpha}$-syn aggregation have been discussed.

Effects of (-)-Sesamin on Memory Deficits in MPTP-lesioned Mouse Model of Parkinson's Disease

  • Zhao, Ting Ting;Shin, Keon Sung;Lee, Myung Koo
    • Natural Product Sciences
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    • v.22 no.4
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    • pp.246-251
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    • 2016
  • This study investigated the effects of (-)-sesamin on memory deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD). MPTP lesion (30 mg/kg/day, 5 days) in mice showed memory deficits including habit learning memory and spatial memory. However, treatment with (-)-sesamin (25 and 50 mg/kg) for 21 days ameliorated memory deficits in MPTP-lesioned mouse model of PD: (-)-sesamin at both doses improved decreases in the retention latency time of the passive avoidance test and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid, improved the decreased transfer latency time of the elevated plus-maze test, reduced the increased expression of N-methyl-D-aspartate (NMDA) receptor, and increased the reduced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB). These results suggest that (-)-sesamin has protective effects on both habit learning memory and spatial memory deficits via the dopaminergic neurons and NMDA receptor-ERK1/2-CREB system in MPTP-lesioned mouse model of PD, respectively. Therefore, (-)-sesamin may serve as an adjuvant phytonutrient for memory deficits in PD patients.

LRRK2 and membrane trafficking: nexus of Parkinson's disease

  • Hur, Eun-Mi;Jang, Eun-Hae;Jeong, Ga Ram;Lee, Byoung Dae
    • BMB Reports
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    • v.52 no.9
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    • pp.533-539
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    • 2019
  • Recent evidence from genetics, animal model systems and biochemical studies suggests that defects in membrane trafficking play an important part in the pathophysiology of Parkinson's disease (PD). Mutations in leucine-rich repeat kinase 2 (LRRK2) constitute the most frequent genetic cause of both familial and sporadic PD, and LRRK2 has been suggested as a druggable target for PD. Although the precise physiological function of LRRK2 remains largely unknown, mounting evidence suggests that LRRK2 controls membrane trafficking by interacting with key regulators of the endosomal-lysosomal pathway and synaptic recycling. In this review, we discuss the genetic, biochemical and functional links between LRRK2 and membrane trafficking. Understanding the mechanism by which LRRK2 influences such processes may contribute to the development of disease-modifying therapies for PD.

Developing an Biomechanical Functional Performance Index for Parkinson's Disease Patients (한국형 파킨슨 환자의 역학적 기능수행지수 개발)

  • Shin, Sunghoon;Han, Byungin;Chung, Chulmin;Lee, Yungon
    • Korean Journal of Applied Biomechanics
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    • v.30 no.1
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    • pp.83-91
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    • 2020
  • Objective: The study aimed to develop a functional performance index that evaluates the functional performance of Parkinson's patients, i.e., to integrate biomechanical measurements of walking, balance, muscle strength and tremor, and to use multiple linear regression with stepwise methods to identify the most suitable predictors for the progression of disease. Method: A total of 60 subjects were tested for sub-variables of four factors: walking, balance, isometric strength and hand tremors. Potential independet variables were extracted through correlation analysis of the sub-variables and dependent variables, Hoehn & Yahr scale. And then, a stepwise multiple regression analysis using the potential independent variables was performed to identify predictor of Hoehn & Yahr scale. Results: First, the results of the study showed that physical composition and gait had a relatively more correlated with the progression of the disease, compared to balance and hand tremor. Second, Parkinson's functional performance is characterized by dynamic pattern of walking, such as foot clearance and turning angle (TA) of walking, and a high-explained regression model is completed. Conclusion: The study emphasized the importance of walking variables and body composition in minor pathological features compared to Parkinson's patient's balancing ability and hand tremor. Specifically, it revealed that dynamic walking patterns functionally characterize patients. The results are worth considering when assessing functional performance related to the progression of the disease at the site.

Neuroprotective Effects of Herbal Ethanol Extracts from Gynostemma pentaphyllum on L-DOPA Therapy in 6-hydroxydopamine-lesioned Rat Model of Parkinson's Disease (돌외 에탄올 추출물 엑스가 6-hydroxydopamine-유도 파킨슨병 백서 모델에서의 L-DOPA 요법에 미치는 영향)

  • Suh, Kwang-Hoon;Choi, Hyun-Sook;Shin, Keon-Seong;Hwang, Bang-Yeon;Lee, Myung-Koo
    • Korean Journal of Pharmacognosy
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    • v.42 no.4
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    • pp.341-347
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    • 2011
  • The neuroprotective effects of herbal ethanol extracts from Gynostemma pentaphyllum (GP-EX) in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease treated with L-DOPA were investigated. Rats were prepared for the Parkinson's disease model by 6-OHDA-lesioning for 14 days. The rats were then treated with L-DOPA (10 and 20 mg/kg) with or without the oral administration of GP-EX (30 mg/kg, daily) for 28 days. L-DOPA (20 mg/kg) treatment for 28 days enhanced dopaminergic neuronal cell death in 6-OHDA-lesioned rat groups, but L-DOPA (10 mg/kg) did not. However, the oral administration of GP-EX (30 mg/kg) for 28 days ameliorated the enhanced neurotoxic effects induced by chronic L-DOPA treatment in 6-OHDA-lesioned rat groups by increasing tyrosine hydroxylase (TH)-immunohistochemical staining and the number of TH-immunopositive cells surviving in the substantia nigra. In addition, GP-EX administration (30 mg/kg) for 28 days recovered the levels of dopamine and norepinephrine of the striatum in 6-OHDA-lesioned rat groups, which were markedly reduced by L-DOPA treatment (20 mg/kg). GP-EX (30 mg/kg) did not produce any signs of toxicity, such as weight loss, diarrhea, or vomiting in rats during the 28-day treatment period. These results suggest that GP-EX has protective functions against chronic L-DOPA-induced neurotoxic reactions in dopaminergic neurons in the 6-OHDA-lesioned rat model of Parkinson's disease. Therefore, GP-EX may be beneficial in the prevention of adverse symptoms in parkisonian patients.

The Effect of Depression on Quality of Life in Patients with Parkinson's Disease: Mediating Effect of Family Function

  • Bae, Eun Sook;Kang, Hye Seung
    • Research in Community and Public Health Nursing
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    • v.33 no.1
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    • pp.105-113
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    • 2022
  • Purpose: The purpose of this study is to explore the roles and function of family in mediating the relationship between depression and quality of life of patients with Parkinson's disease (PD). Most studies have found that depression is particularly common in patients with PD and further associated with poor quality of life. Family function, as a mediator, is based on a strength orientation perspective that emphasizes not only their responsibilities and risks but also recuperative powers and growth potential. Methods: Overall 157 adults with idiopathic Parkinson's disease were enrolled in this study via outpatient clinic and completed a set of assessment to measure depression using BDI, family APGAR questionnaire, and patients' quality of life using PDQ-8. Hierarchical multiple regression analysis was conducted to examine the mediating role of family APGAR score in the relationship between BDI and PDQ-8. Results: Patients' depression, gait disturbance, duration of illness, and family function were statistically significant on quality of life. These factors accounted for 60% of the variance in quality of life. Family function has a partial mediating effect on the relationship between depression and quality of life. Conclusion: Findings from the study suggest that although PD patients' depression impacts their quality of life, by having strong family function, the extent to which depression impacts the quality of life can be favorably mitigated. Additionally, these outcomes have important implications for future model development regarding PD patients.