• Title/Summary/Keyword: Amyotrophic lateral sclerosis(ALS)

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Transduced HSP27 protein protects neuronal cell death by enhancing FALS-associated SOD1 mutant activity

  • An, Jae-Jin;Lee, Yeom-Pyo;Kim, Dae-Won;Sohn, Eun-Joung;Jeong, Hoon-Jae;Kang, Hye-Won;Shin, Min-Jae;Kim, Mi-Jin;Ahn, Eun-Hee;Jang, Sang-Ho;Kang, Jung-Hoon;Kang, Tae-Cheon;Won, Moo-Ho;Kwon, Oh-Shin;Cho, Sung-Woo;Lee, Kil-Soo;Park, Jin-Seu;Eum, Won-Sik;Choi, Soo-Young
    • BMB Reports
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    • v.42 no.3
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    • pp.136-141
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    • 2009
  • Familial Amyotrophic lateral sclerosis (FALS) is a progressive neurodegenetative disorder induced by mutations of the SOD1 gene. Heat shock protein 27 (HSP27) is well-defined as a stress-inducible protein, however the its role in ALS protection has not yet been established. To investigate the role HSP27 may have in SOD1 mutant-mediated apoptosis, human SOD1 or HSP27 genes were fused with a PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame fusion protein, which was then transduced into cells. We found the purified PEP-1-HSP27 fusion proteins can be transduced efficiently into neuronal cells and protect against cell death by enhancing mutant SOD1 activity. Moreover, transduced PEP-1-HSP27 efficiently prevents protein aggregation produced by oxidative stress. These results suggest that transduced HSP27 fusion protein may be explored as a potential therapeutic agent for FALS patients.

Ghrelin Protects Spinal Cord Motoneurons Against Chronic Glutamate Excitotoxicity by Inhibiting Microglial Activation

  • Lee, Sung-Youb;Kim, Yu-Mi;Li, Endan;Park, Seung-Joon
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.1
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    • pp.43-48
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    • 2012
  • Glutamate excitotoxicity is emerging as a contributor to degeneration of spinal cord motoneurons in amyotrophic lateral sclerosis (ALS). Recently, we have reported that ghrelin protects motoneurons against chronic glutamate excitotoxicity through the activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-$3{\beta}$ pathways. Previous studies suggest that activated microglia actively participate in the pathogenesis of ALS motoneuron degeneration. However, it is still unknown whether ghrelin exerts its protective effect on motoneurons via inhibition of microglial activation. In this study, we investigate organotypic spinal cord cultures (OSCCs) exposed to threohydroxyaspartate (THA), as a model of excitotoxic motoneuron degeneration, to determine if ghrelin prevents microglial activation. Exposure of OSCCs to THA for 3 weeks produced typical motoneuron death, and treatment of ghrelin significantly attenuated THA-induced motoneuron loss, as previously reported. Ghrelin prevented THA-induced microglial activation in the spinal cord and the expression of pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ and interleukin-$1{\beta}$. Our data indicate that ghrelin may act as a survival factor for motoneurons by functioning as a microglia-deactivating factor and suggest that ghrelin may have therapeutic potential for the treatment of ALS and other neurodegenerative disorders where inflammatory responses play a critical role.

Communication Support System for Person with Language Disabilities (중증 언어장애인을 위한 의사소통 시스템)

  • Hong Seung-Wook;Park Su-Hyun
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2006.05a
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    • pp.324-327
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    • 2006
  • The person who gets a ALS(Amyotrophic Lateral Sclerosis) has language disability and physical disability together. A common first symptom is a painless weakness in a hand, foot, arm or leg, which occurs in more than half of all cases. Other early symptoms include muscle weakness of speech. In the early stage of this disease they can communicate with other persons, but it will become increasingly difficult. In our research we have designed and implemented communication tools for them. We have implemented Chunjiin(the Korean computer keyboard) at PDA(personal digital assistant). And we have also implemented software which is consisted of frequently used words.

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CHIP promotes the degradation of mutant SOD1 by reducing its interaction with VCP and S6/S6' subunits of 26S proteasome

  • Choi, Jin-Sun;Lee, Do-Hee
    • Animal cells and systems
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    • v.14 no.1
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    • pp.1-10
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    • 2010
  • Previously we showed that CHIP, a co-chaperone of Hsp70 and E3 ubiquitin ligase, can promote the degradation of mutant SOD1 linked to familial amyotrophic lateral sclerosis (fALS) via a mechanism not involving SOD1 ubiquitylation. Here we present evidence that CHIP functions in the interaction of mutant SOD1 with 26S proteasomes. Bag-1, a coupling factor between molecular chaperones and the proteasomes, formed a complex with SOD1 in an hsp70-dependent manner but had no direct effect on the degradation of mutant SOD1. Instead, Bag-1 stimulated interaction between CHIP and the proteasome-associated protein VCP (p97), which do not associate normally. Over-expressed CHIP interfered with the association between mutant SOD1 and VCP. Conversely, the binding of CHIP to mutant SOD1 was inhibited by VCP, implying that the chaperone complex and proteolytic machinery are competing for the common substrates. Finally we observed that mutant SOD1 strongly associated with the 19S complex of proteasomes and CHIP over-expression specifically reduced the interaction between S6/S6' ATPase subunits and mutant SOD1. These results suggest that CHIP, together with ubiquitin-binding proteins such as Bag-1 and VCP, promotes the degradation of mutant SOD1 by facilitating its translocation from ATPase subunits of 19S complex to the 20S core particle.

Implementation to human-computer interface system with motion tracking using OpenCV and FPGA (FPGA와 OpenCV를 이용한 눈동자 모션인식을 통한 의사소통 시스템)

  • Lee, Hee Bin;Heo, Seung Won;Lee, Seung Jun;Yu, Yun Seop
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2018.05a
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    • pp.696-699
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    • 2018
  • This paper introduces a system that enables pupillary tracing and communication with patients with amyotrophic lateral sclerosis (ALS) who can not move free. Face and pupil are tracked using OpenCV, and eye movements are detected using DE1-SoC board. We use the webcam, track the pupil, identify the pupil's movement according to the pupil coordinate value, and select the character according to the user's intention. We propose a system that can use relatively low development cost and FPGA can be reusable, and can select a text easily to mobile phone by using Bluetooth.

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A Case of Therapeutic Laser for Suggested Drug Induced Liver Injury Patient during Treatment of Korean Medicine (한방치료 중 약인성 간손상으로 추정되는 환자에 대한 치료레이저 치험 1례)

  • Lim, Kyeong-Tae;Shin, Byung-Cheul;Hwang, Eui-Hyoung;Heo, In;Kim, Byung-Jun;Heo, Kwang-Ho
    • Journal of Korean Medicine Rehabilitation
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    • v.26 no.3
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    • pp.183-189
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    • 2016
  • A 84 year old male patient with amyotrophic lateral sclerosis (ALS) was treated by Jeungsonbaekchulsan and Gakbyeongyeonsu-tang for ten days. In the course of treatments, this patient was evaluated with Roussel Uclaf Casusality Assessment Method (RUCAM), showing results of drug induced liver injury. Herb medicine was immediately discontinued, followed by therapeutic laser treatments once a day for one week combined with 2 weeks of GODEX$^{(R)}$ administration. Transaminase results were lowered and changes in blood test results were time-effective changes. Therapeutic laser therapy could be considered effective on drug induced liver injury with further studies.

Expression of Human SOD1 and Mutant SOD1 (G93A) in E. coli and Identification of SOD1 as a Substrate of HtrA2 Serine Protease (대장균에서의 human SOD1과 mutant SOD1 (G93A) 단백질의 발현과 HtrA2의 기질 여부 확인에 관한 연구)

  • Kim, Goo-Young;Kim, Sang-Soo;Park, Hyo-Jin;Rhim, Hyang-Shuk
    • Journal of Life Science
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    • v.16 no.5
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    • pp.716-722
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    • 2006
  • Superoxide dismutase (SOD) is physiologically important in regulating cellular homeostasis and apoptotic cell death, and its mutations are the cause of familial amyotrophic lateral sclerosis (FALS). Mitochondrial serine protease HtrA2 has a pro-apoptotic function and has known to be associated with neurodegenerative disorders. To investigate the relationship between genes associated with apoptotic cell death, such as HtrA2 and SOD1, we utilized the pGEX expression system to develop a simple and rapid method for purifying wild-type and ALS-associated mutant SOD1 proteins in a suitable form for biochemical studies. We purified SOD1 and SOD1 (G93A) proteins to approximately 90% purity with relatively high yields (3 mg per liter of culture). Consistent with the result in mammalian cells, SOD1 (G93A) was more insoluble than wild-type SOD1 in E. coli, indicating that research on the aggregate formation of SOD1 may be possible using this pGEX expression system in E. coli. We investigated the HtrA2 serine protease activity on SOD1 to assess the relationship between two proteins. Not only wild-type SOD1 but also ALS-associated mutant SOD1 (G93A) were cleaved by HtrA2, resulting in the production of the 19 kDa and 21 kDa fragments that were specific for anti-SOD1 antibody. Using protein gel electrophoresis and immunoblot assay, we compared the relative molecular masses of thrombin-cleaved GST-SOD1 and HtrA2-cleaved SOD1 fragments and can predict that the HtrA2-cleavage sites within SOD1 are the peptide bonds between leucine 9-lysine 10 (L9-K10) and glutamine 23-lysine 24 (Q23-K24). Our study indicates that SOD1 is one of the substrate for HtrA2, suggesting that both HtrA2 and SOD1 may be important for modulating the HtrA2-SOD1-mediated apopotic cell death that is associated with the pathogenesis of neurodegenerative disorder.

Effect of Bee Venom on Glutamate-mediated Excitotoxicity in NSC-34 Motor Neuronal Cells (Glutamate 매개 흥분성 신경독성에 대한 봉독의 NSC-34 신경세포사멸 억제 효과)

  • Lee, Sang-Min;Choi, Sun-Mi;Jung, So-Young;Yang, Eun-Jin
    • YAKHAK HOEJI
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    • v.55 no.5
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    • pp.385-390
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    • 2011
  • Bee venom (BV), which is extracted from honeybees, has been used in traditional Korean medical therapy. Glutamate-mediated excitotoxicity contributes to neuronal death in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) or Alzheimer's disease (AD). This study is to investigate the effect of BV on glutamate-induced neurotoxicity on NSC-34 motor neuron cells. To determine the viability of motor neuronal cells, we performed with MTT assays in glutamate-treated NSC-34 cell with BV or without. For the measurement of oxidative stress, DCF assay was used in glutamate-treated NSC-34 motor neuronal cells with BV or without. To investigate the molecular mechanism of BV against glutamate-mediated neurotoxicity in NSC-34 cells, western blot analysis was used. Glutamate significantly decreased cell viability by glutamate dose- or treatment time-dependent manner in NSC-34 cells. However, BV pre-treatment dramatically inhibited glutamate-induced neuronal cell death. Furthermore, we found that BV increased the expression of Bcl-2 protein that is anti-apoptotic protein and reduced the generation of oxidative stress. BV has a neuroprotective role against glutamate neurotoxicity by an increase of anti-apoptotic protein. It suggests that BV may be useful for the reduction of neuronal cell death in neuronal disease models.

Design of Computer Access Devices for Severly Motor-disability Using Bio-potentials (생체전위를 이용한 중증 운동장애자들을 위한 컴퓨터 접근제어장치 설계)

  • Jung, Sung-Jae;Kim, Myung-Dong;Park, Chan-Won;Kim, Il-Hwan
    • The Transactions of the Korean Institute of Electrical Engineers D
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    • v.55 no.11
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    • pp.502-510
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    • 2006
  • In this paper, we describe implementation of a computer access device for the severly motor-disability. Many people with severe motor disabilities need an augmentative communication technology. Those who are totally paralyzed, or 'locked-in' cannot use conventional augmentative technologies, all of which require some measure of muscle control. The forehead is often the last site to suffer degradation in cases of severe disability and degenerative disease. For example, In ALS(Amyotrophic Lateral Sclerosis) and MD(Muscular dystrophy) the ocular motorneurons and ocular muscles are usually spared permitting at least gross eye movements, but not precise eye pointing. We use brain and body forehead bio-potentials in a novel way to generate multiple signals for computer control inputs. A bio-amplifier within this device separates the forehead signal into three frequency channels. The lowest channel is responsive to bio-potentials resulting from an eye motion, and second channel is the band pass derived between 0.5 and 45Hz, falling within the accepted Electroencephalographic(EEG) range. A digital processing station subdivides this region into eleven components frequency bands using FFT algorithm. The third channel is defined as an Electromyographic(EMG) signal. It responds to contractions of facial muscles and is well suited to discrete on/off switch closures, keyboard commands. These signals are transmitted to a PC that analyzes in a time series and a frequency region and discriminates user's intentions. That software graphically displays user's bio-potential signals in the real time, therefore user can see their own bio-potentials and control their physiological signals little by little after some training sessions. As a result, we confirmed the performance and availability of the developed system with experimental user's bio-potentials.

Probabilistic exposure assessment, a risk-based sampling plan and food safety performance evaluation of common vegetables (tomato and brinjal) in Bangladesh

  • Mazumder, Mohammad Nurun-Nabi;Bo, Aung Bo;Shin, Seung Chul;Jacxsens, Liesbeth;Akter, Tahmina;Bir, Md. Shahidul Haque;Aktar, Most Mohshina;Rahman, Md. Habibur;WeiQiang, Jia;Park, Kee Woong
    • Korean Journal of Agricultural Science
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    • v.48 no.1
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    • pp.33-43
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    • 2021
  • Along with the widespread use of pesticides in the world, concerns over human health impacts are rapidly growing. There is a large body of evidence on the relationship between the exposure to pesticides and the elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. This research assessed the health risk of pesticide residues by the dietary intake of vegetables collected from the agro-based markets of Dhaka, Bangladesh. As some of the banned pesticides were also found in vegetable samples, they may pose a higher risk because of cheaper availability and hence the government of Bangladesh should take strong measures to control these banned pesticides. Five organo phosphorus (chlorpyrifos, parathion, ethion, acephate, fenthion) and two carbamate (carbaryl and carbofuran) pesticide residues were identified in twenty four samples of two common vegetables (tomato and brinjal). The pesticide residues ranged from below a detectable limit (< 0.01) to 0.36 mg·kg-1. Acephate, chlorpyrifos, ethion, and carbaryl were detected in only one sample, while co-occurrence occurred twice for parathion. Continuous monitoring and strict regulation should be enforced regarding the control of pesticide residues in fresh vegetables and other food commodities in Bangladesh.