• Journal of Radiopharmaceuticals and Molecular Probes
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• v.9 no.1
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• pp.3-8
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• 2023

Parkinson's disease is a neurodegenerative disease caused by damage to brain neurons related to dopamine. Non-clinical animal models mainly used in Parkinson's disease research include drug-induced models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine, and genetically modified transgenic animal models. Parkinson's diagnosis can be made using brain imaging of the substantia nigra-striatal dopamine system and using a radiotracer that specifically binds to the dopamine transporter. In this study, ¹⁸F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane was used to confirm the image evaluation cutoff between normal and parkinson's disease models, and to confirm model persistence over time. In addition, the efficacy of single or combined administration of clinically used therapeutic drugs in parkinson's animal models was evaluated. Image analysis was performed using the PMOD software. Converted to standardized uptake value, and analyzed by standardized uptake value ratio by dividing the average value of left striatum by the average value of right striatum obtained by applying positron emission tomography images to the atlas magnetic resonance template. The image cutoff of the normal and the parkinson's disease model was calculated as SUVR=0.829, and it was confirmed that it was maintained during the test period. In the three-drug combination administration group, the right and left striatum showed a high symmetry of more than 0.942 on average and recovered significantly. Images using ¹⁸F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane are thought to be able to diagnose and evaluate treatment efficacy of non-clinical Parkinson's disease.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.49-52
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• 2008

Parkinson's disease is characterized by motor disturbances and dopaminergic neurodegeneration. parkin and PINK1, two most critical Parkinson's disease-associated genes, have been intensively studied to address the underlying molecular pathogenesis of the disease, but our understanding still remains unclear. Through generation and characterization of Drosophila mutants for PINK1, we show that PINK1 is required for mitochondrial integrity and function in both indirect flight muscles and dopaminergic neurons. Surprisingly, we find that PINK1 mutants share striking phenotypic similarities with parkin mutants. Indeed, transgenic expression of parkin dramatically ameliorates all PINK1 loss-of-function phenotypes, but not vice versa, implicating that Parkin acts downstream of PINK1 in maintaining mitochondrial integrity and function in both muscles and dopaminergic neurons. With the establishment of the PINK1-Parkin pathway, we are trying to further investigate the detailed molecular relationship between PINK1 and Parkin using both mammalian dopaminergic neuronal cells for biochemical analysis and Drosophila model animal for genetic analysis. We believe that elucidating the molecular function of Parkinson's disease-associated genes will be of big help for the ultimate understanding of the pathogenic mechanism of this disease and also for the development of effective drugs for Parkinson's disease.

• BMB Reports
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• v.47 no.8
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• pp.424-432
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• 2014

The defining feature of Parkinson's disease is a progressive and selective demise of dopaminergic neurons. A recent report on Parkinson's disease animal model demonstrates that poly (ADP-ribose) (PAR) dependent cell death, also named parthanatos, is accountable for selective dopaminergic neuronal loss. Parthanatos is a programmed necrotic cell death, characterized by PARP1 activation, apoptosis inducing factor (AIF) nuclear translocation, and large scale DNA fragmentation. Besides cell death regulation via interaction with AIF, PAR molecule mediates diverse cellular processes including genomic stability, cell division, transcription, epigenetic regulation, and stress granule formation. In this review, we will discuss the roles of PARP1 activation and PAR molecules in the pathological processes of Parkinson's disease. Potential interaction between PAR molecule and Parkinson's disease protein interactome are briefly introduced. Finally, we suggest promising points of therapeutic intervention in the pathological PAR signaling cascade to halt progression in Parkinson's disease.

• Proceedings of the KSAR Conference
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• 2004.06a
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• pp.274-274
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• 2004

The purpose of this study is to evaluate the efficacy of in vitro differentiated human embryonic stem (MB03) cells expressing Nurr1 in relief of symptomatic motor behavior of Parkinson's disease (PD) animal models. MB03 cell was genetically modified to express Nurr1 protein (Nr#24/MB03) and was induced to differentiate according to 2- /4+ protocol using retinoic acid and ascorbic acid. (omitted)

• Journal of Microbiology and Biotechnology
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• v.32 no.9
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• pp.1168-1177
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• 2022

Parkinson's disease (PD) is the second-most prevalent neurodegenerative disease and is characterized by dopaminergic neuronal death in the midbrain. Recently, the association between alterations in PD pathology and the gut microbiota has been explored. Microbiota-targeted interventions have been suggested as a novel therapeutic approach for PD. Agathobaculum butyriciproducens SR79^T (SR79) is an anaerobic bacterium. Previously, we showed that SR79 treatment induced cognitive improvement and reduced Alzheimer's disease pathologies in a mouse model. In this study, we hypothesized that SR79 treatment may have beneficial effects on PD pathology. To investigate the therapeutic effects of SR79 on PD, 6-hydroxydopamine (6-OHDA)-induced mouse models were used. D-Amphetamine sulfate (d-AMPH)-induced behavioral rotations and dopaminergic cell death were analyzed in unilateral 6-OHDA-lesioned mice. Treatment with SR79 significantly decreased ipsilateral rotations induced by d-AMPH. Moreover, SR79 treatment markedly activated the AKT/GSK3β signaling pathway in the striatum. In addition, SR79 treatment affected the Nrf2/ARE signaling pathway and its downstream target genes in the striatum of 6-OHDA-lesioned mice. Our findings suggest a protective role of SR79 in 6-OHDA-induced toxicity by regulating the AKT/Nrf2/ARE signaling pathway and astrocyte activation. Thus, SR79 may be a potential microbe-based intervention and therapeutic strategy for PD.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2004.10a
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• pp.98-99
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• 2004

• 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.

• 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.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.103-103
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• 2003

The purpose of this study is to evaluate an efficacy of in vitro differentiated human embryonic stem (hES, MB03) cells expressing Nurr1 in relief of symptomatic motor behavior of Parkinson's disease (PD) animal models MB03 was genetically modified to express Nurr1 protein and was induced to differentiate according to 2-/4+ protocol using retinoic acid and ascorbic acid. The differentiation-induced cells were selected for 10 to 20 days thereafter in N2 medium. Upon selection, cells expressing GFAP, TH, or NF200 were 38.8%, 11%, and 20.5%, respectively. in order to examine therapeutic effects of the differentiated cells in PD animal model, rats were unilaterally lesioned by administration of 6-kydroxydopamine HCI (6-OHDA) into medial forebrain region (MFB, AP -4.4 mm, ML 1.2 mm, DV 78 mm with incision bar set at -2.4 mm), as a reference to bregma and the surface of the skull. Confirmation of successful lesion by apomorphine-induced rotational behavior, differentiated cells were transplanted into the striatum (AP 1.0, ML 3.5, DV -5.0; AP 0.6, ML 2.5, DV -4.5). Improvements of asymmetric motor behavior by the transplantation were examined every two weeks after the surgery. In two weeks, numbers of rotation by the experimental rats were $-14.8 \pm 33.9%$ (P<0.05) of the number before transplantation, however, the ratio increased slightly to $13.6 \pm 56.3%$ in six weeks. In contrast, the ratio of sham-grafted animals ranged from 112.3+8.5% to 139.2+28.9% during the examination. Immunohistochemical studies further confirmed the presence, survival, migration, and expression of TH of the transplanted human cells.

• The Journal of Internal Korean Medicine
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• v.41 no.6
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• pp.993-1014
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• 2020

Objective: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Antioxidant stress and inflammatory reactions are important causes of neurodegenerative diseases and are major causes of PD. Many animal experiments have been aimed at treating PD using the antioxidant effects of various traditional medicines and dietary supplements. This review reports the research investigating the antioxidant effects of herbs in in vivo PD models. Methods: The study consisted of a database search for articles related to PD and herbal treatments using the OASIS, NDSL, KTKP, Korean KISS, PubMed, Science Direct, CNKI, Wanfang, and J-STAGE databases. The search period was limited from the start of the search engine application to November 14, 2019. Studies were selected to confirm the antioxidant effects of herbal medicines in an in vivo PD model. Results: Eighty-two studies were summarized for plant species, extracts (or compounds), animal models, neurotoxins, and functional results. The most frequently used herbal materials were Bacopa monnieri, Camellia sinensis, Centella asiatica, and Withania somnifera. MPTP and 6-OHDA were the most commonly used neurotoxins for inducing PD. Most studies confirmed an increased expression and activation of antioxidant enzymes and a decrease in oxidative stress. Herbal materials showed their antioxidant effects regardless of the order of treatment and confirmed their possible use as treatments for the prevention and treatment of neurodegeneration. Conclusion: Many herbal medicines have antioxidant effects and are likely to be effective in delaying neurodegenerative damage by inhibiting or reducing oxidative stress by expression of antioxidant enzymes.