• Bulletin of the Korean Chemical Society
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• v.34 no.2
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• pp.665-668
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• 2013

• BMB Reports
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• v.50 no.7
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• pp.345-354
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• 2017

Autophagy, a catabolic process necessary for the maintenance of intracellular homeostasis, has recently been the focus of numerous human diseases and conditions, such as aging, cancer, development, immunity, longevity, and neurodegeneration. However, the continued presence of autophagy is essential for cell survival and dysfunctional autophagy is thought to speed up the progression of neurodegeneration. The actual molecular mechanism behind the progression of dysfunctional autophagy is not yet fully understood. Emerging evidence suggests that basal autophagy is necessary for the removal of misfolded, aggregated proteins and damaged cellular organelles through lysosomal mediated degradation. Physiologically, neurodegenerative disorders are related to the accumulation of amyloid ${\beta}$ peptide and ${\alpha}-synuclein$ protein aggregation, as seen in patients with Alzheimer's disease and Parkinson's disease, respectively. Even though autophagy could impact several facets of human biology and disease, it generally functions as a clearance for toxic proteins in the brain, which contributes novel insight into the pathophysiological understanding of neurodegenerative disorders. In particular, several studies demonstrate that natural compounds or small molecule autophagy enhancer stimuli are essential in the clearance of amyloid ${\beta}$ and ${\alpha}-synuclein$ deposits. Therefore, this review briefly deliberates on the recent implications of autophagy in neurodegenerative disorder control, and emphasizes the opportunities and potential therapeutic application of applied autophagy.

• Journal of Microbiology and Biotechnology
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• v.27 no.4
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• pp.718-724
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• 2017

The combination of rabies immunoglobulin (RIG) with a vaccine is currently effective against rabies infections, but improvements are needed. Genetic engineering antibody technology is an attractive approach for developing novel antibodies to replace RIG. In our previous study, a single-chain variable fragment, scFv57R, against rabies virus glycoprotein was constructed. However, its inherent weak stability and short half-life compared with the parent RIG may limit its diagnostic and therapeutic application. Therefore, an acidic tail of synuclein (ATS) derived from the C-terminal acidic tail of human alpha-synuclein protein was fused to the C-terminus of scFv57R in order to help it resist adverse stress and improve the stability and half-life. The tail showed no apparent effect on the preparation procedure and affinity of the protein, nor did it change the neutralizing potency in vitro. In the ELISA test of molecular stability, the ATS fusion form of the protein, scFv57R-ATS, showed an increase in thermal stability and longer half-life in serum than scFv57R. The protection against fatal rabies virus challenge improved after fusing the tail to the scFv, which may be attributed to the improved stability. Thus, the ATS fusion approach presented here is easily implemented and can be used as a new strategy to improve the stability and half-life of engineered antibody proteins for practical applications.

• Biomolecules & Therapeutics
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• v.19 no.1
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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.

• Journal of the Korean Applied Science and Technology
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• v.37 no.4
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• pp.744-754
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• 2020

We investigated the whether endurance exercise and MitoQ intake mediated neuroprotection are associated with mitochondrial function in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine(MPTP) -induced mice model of Parkinson's disease. C57BL/6 male mice were randomly assigned to five groups: Normal Conrol(NC, n=10), MPTP Control(MC, n=10), MPTP +MitoQ(MQ, n=10), MPTP + Exercise(ME, n=10) and MPTP + MitoQ + Exercise(MQE, n=10). Exercise intervention groups performed the treadmill exercise for 5days/week for 5 weeks with gradual increase of intensity. MitoQ intake groups consumed the MitoQ at a concentration of 250μmol by dissolving with water during experiment period. Our data demonstrated that ME and MQE group restored MPTP-induced motor dysfunction. In addition, treatment groups(MQ, ME and MQE) increased tyrosine hydroxylase levels, and suppressed the accumulation of α-synuclein levels. Futhermore, treatment groups modulated the mitochondrial function such as upregulated mitochondrial biogenesis, increased antioxidant enzyme, enhanced a anti-apoptotic protein(e.g., BCL2), and reduced a pro-apoptotic protein(e.g., BAX). Taken together, these results suggested that endurance exercise and MitoQ intake-mediated increase in mitochondrial function contributes to improvement of aggravated dopaminergic neuronal, resulting in attenuation of motor function of Parkinson's disease.

• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.350-357
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• 2018

Glial cells are receiving much attention since they have been recognized as important regulators of many aspects of brain function and disease. Recent evidence has revealed that two different glial cells, astrocytes and microglia, control synapse elimination under normal and pathological conditions via phagocytosis. Astrocytes use the MEGF10 and MERTK phagocytic pathways, and microglia use the classical complement pathway to recognize and eliminate unwanted synapses. Notably, glial phagocytosis also contributes to the clearance of disease-specific protein aggregates, such as ${\beta}$-amyloid, huntingtin, and ${\alpha}$-synuclein. Here we reivew recent findings showing that glial cells are active regulators in brain functions through phagocytosis and that changes in glial phagocytosis contribute to the pathogenesis of various neurodegenerative diseases. A better understanding of the cellular and molecular mechanisms of glial phagocytosis in healthy and diseased brains will greatly improve our current approach in treating these diseases.

• Proceedings of the Korea Information Processing Society Conference
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• 2014.04a
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• pp.753-756
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• 2014

파킨슨병은 도파민계 신경이 파괴되는 질병으로 알츠하이머병과 함께 대표적인 퇴행성 뇌 질환으로 병의 진행을 완화시킬 수 있는 치료법이 존재하기 때문에 병의 진단이 굉장히 중요하다. 파킨슨병을 진단하기 위한 과거의 연구는 대부분 단일 생체지표를 이용하는 것이었지만 이러한 방법에는 한계성이 존재한다. 따라서 본 연구에서는 생화학적 생체지표인 뇌척수액 내의 ${\alpha}-synuclein$ 단백질 수치와 영상학적 생체지표인 확산 텐서 영상의 여러 모수들을 결합한 융합 생체지표를 특징으로 사용하는 파킨슨병 진단 모델을 개발하고 성능을 평가하였다. 10-fold cross validation 에서 모든 성능지표에 대해 최고 100%를 보였으며, cross validation 의 과적합을 감안하더라도 파킨슨병의 조기진단에 유용하게 사용될 수 있는 가능성을 제시하였다.

• Journal of the Korean Applied Science and Technology
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• v.41 no.1
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• pp.58-68
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• 2024

The purpose of this study was to investigate the effects of treadmill exercise treadmill exercise (TE) and environmental enrichment (EE) interventions on cognitive function, muscle function, and the expression of tight junction proteins in an Alzheimer's disease (AD) animal model. To create the AD animal model, aluminum chloride (AlCl₃) was administered for 90 days (40mg/kg/day), while simultaneously exposing the animals to TE (10-12m/min, 40-60min/day) or EE. The results showed that cognitive impairment and muscle dysfunction induced by AlCl₃ administration were alleviated by TE and EE. Furthermore, TE and EE reduced the increased expression of β-amyloid(Aβ), alpha-synuclein, and tumor necrosis factor-α (TNF-α) proteins observed in AD pathology. Additionally, TE and EE significantly increased the expression of decreased adhesive adjacent proteins (Occludin, Claudin-5, and ZO-1) induced by AlCl₃ administration. Lastly, correlation analysis between Aβ protein and tight junction proteins showed negative correlations (Occludin: r=-0.853, p=0.001; Claudin-5: r=-0.352, p=0.915; ZO-1: r=-0.424, p=0.0390). In conclusion, TE or EE interventions are considered effective exercise methods that partially alleviate pathological features of AD, improving cognitive and muscle function.

• BMB Reports
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• v.42 no.9
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• pp.541-551
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• 2009

Amyloidogenesis defines a condition in which a soluble and innocuous protein turns to insoluble protein aggregates known as amyloid fibrils. This protein suprastructure derived via chemically specific molecular self-assembly process has been commonly observed in various neurodegenerative disorders such as Alzheimer's, Parkinson's, and Prion diseases. Although the major culprit for the cellular degeneration in the diseases remains unsettled, amyloidogenesis is considered to be etiologically involved. Recent recognition of fibrillar polymorphism observed mostly from in vitro amyloidogeneses may indicate that multiple mechanisms for the amyloid fibril formation would be operated. Nucleation-dependent fibrillation is the prevalent model for assessing the self-assembly process. Following thermodynamically unfavorable seed formation, monomeric polypeptides bind to the seeds by exerting structural adjustments to the template, which leads to accelerated amyloid fibril formation. In this review, we propose another in vitro model of amyloidogenesis named double-concerted fibrillation. Here, two consecutive assembly processes of monomers and subsequent oligomeric species are responsible for the amyloid fibril formation of $\alpha$-synuclein, a pathological component of Parkinson's disease, following structural rearrangement within the oligomers which then act as a growing unit for the fibrillation.

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.133-143
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• 2012

Matrix metalloproteinases (MMPs) are a subfamily of zinc-dependent proteases that are re-sponsible for degradation and remodeling of extracellular matrix proteins. The activity of MMPs is tightly regulated at several levels including cleavage of prodomain, allosteric activation, com-partmentalization and complex formation with tissue inhibitor of metalloproteinases (TIMPs). In the central nervous system (CNS), MMPs play a wide variety of roles ranging from brain devel-opment, synaptic plasticity and repair after injury to the pathogenesis of various brain disorders. Following general discussion on the domain structure and the regulation of activity of MMPs, we emphasize their implication in various brain disorder conditions such as Alzheimer's disease, multiple sclerosis, ischemia/reperfusion and Parkinson's disease. We further highlight accumu-lating evidence that MMPs might be the culprit in Parkinson's disease (PD). Among them, MMP-3 appears to be involved in a range of pathogenesis processes in PD including neuroinflamma-tion, apoptosis and degradation of ${\alpha}$-synuclein and DJ-1. MMP inhibitors could represent poten-tial novel therapeutic strategies for treatments of neurodegenerative diseases.