• 제목/요약/키워드: Parkinson's Diseases

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Critical Roles of Deubiquitinating Enzymes in the Nervous System and Neurodegenerative Disorders

  • Das, Soumyadip;Ramakrishna, Suresh;Kim, Kye-Seong
    • Molecules and Cells
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    • v.43 no.3
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    • pp.203-214
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    • 2020
  • Post-translational modifications play major roles in the stability, function, and localization of target proteins involved in the nervous system. The ubiquitin-proteasome pathway uses small ubiquitin molecules to degrade neuronal proteins. Deubiquitinating enzymes (DUBs) reverse this degradation and thereby control neuronal cell fate, synaptic plasticity, axonal growth, and proper function of the nervous system. Moreover, mutations or downregulation of certain DUBs have been found in several neurodegenerative diseases, as well as gliomas and neuroblastomas. Based on emerging findings, DUBs represent an important target for therapeutic intervention in various neurological disorders. Here, we summarize advances in our understanding of the roles of DUBs related to neurobiology.

Design of Novel JNK3 Inhibitors Based on 3D-QSAR In Silico Model

  • Madhavan, Thirumurthy
    • Journal of Integrative Natural Science
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    • v.5 no.1
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    • pp.6-12
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    • 2012
  • c-Jun N-terminal kinase-3 (JNK-3) has been identified as a promising target for neuronal apoptosis and has the effective therapeutic for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and other CNS disorders. Herein, we report the essential structural and chemical parameters for JNK-3 inhibitors utilizing comparative molecular field similarity indices analysis (CoMSIA) using the derivatives of 3,5-disubstituted quinolines. The best predictions were obtained CoMSIA model (q2=0.834, r2=0.987) and the statistical parameters from the generated 3D-QSAR models were indicated that the data are well fitted and have high predictive ability. The resulting contour map from 3D-QSAR models might be helpful to design novel and more potent JNK3 derivatives.

Epicatechin Prevents Methamphetamine-Induced Neuronal Cell Death via Inhibition of ER Stress

  • Kang, Youra;Lee, Ji-Ha;Seo, Young Ho;Jang, Jung-Hee;Jeong, Chul-Ho;Lee, Sooyeun;Jeong, Gil-Saeng;Park, Byoungduck
    • Biomolecules & Therapeutics
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    • v.27 no.2
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    • pp.145-151
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    • 2019
  • Methamphetamine (METH) acts strongly on the nervous system and damages neurons and is known to cause neurodegenerative diseases such as Alzheimer's and Parkinson's. Flavonoids, polyphenolic compounds present in green tea, red wine and several fruits exhibit antioxidant properties that protect neurons from oxidative damage and promote neuronal survival. Especially, epicatechin (EC) is a powerful flavonoid with antibacterial, antiviral, antitumor and antimutagenic effects as well as antioxidant effects. We therefore investigated whether EC could prevent METH-induced neurotoxicity using HT22 hippocampal neuronal cells. EC reduced METH-induced cell death of HT22 cells. In addition, we observed that EC abrogated the activation of ERK, p38 and inhibited the expression of CHOP and DR4. EC also reduced METH-induced ROS accumulation and MMP. These results suggest that EC may protect HT22 hippocampal neurons against METH-induced cell death by reducing ER stress and mitochondrial damage.

Development of ML and IoT Enabled Disease Diagnosis Model for a Smart Healthcare System

  • Mehra, Navita;Mittal, Pooja
    • International Journal of Computer Science & Network Security
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    • v.22 no.7
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    • pp.1-12
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    • 2022
  • The current progression in the Internet of Things (IoT) and Machine Learning (ML) based technologies converted the traditional healthcare system into a smart healthcare system. The incorporation of IoT and ML has changed the way of treating patients and offers lots of opportunities in the healthcare domain. In this view, this research article presents a new IoT and ML-based disease diagnosis model for the diagnosis of different diseases. In the proposed model, vital signs are collected via IoT-based smart medical devices, and the analysis is done by using different data mining techniques for detecting the possibility of risk in people's health status. Recommendations are made based on the results generated by different data mining techniques, for high-risk patients, an emergency alert will be generated to healthcare service providers and family members. Implementation of this model is done on Anaconda Jupyter notebook by using different Python libraries in it. The result states that among all data mining techniques, SVM achieved the highest accuracy of 0.897 on the same dataset for classification of Parkinson's disease.

Current research status for imaging neuroinflammation by PET

  • Namhun Lee;Jae Yong Choi
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.6 no.2
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    • pp.116-130
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    • 2020
  • The aging society is globally one of biggest issue because it is related with various degenerative brain disease such as dementia, Parkinson's disease, Alzheimer's disease, multiple sclerosis, and cerebrovascular disease. These diseases are characterized by misfolded-protein aggregation; another pathological trait is "neuroinflammation". In physiological state, the resting microglia cells are activated and it removes abnormal synapses and cell membrane debris to maintain the homeostasis. In pathological state, however, microglia undergo morphological change form 'resting' to 'activated amoeboid phenotype' and the microglia cells are accumulated by neuronal damage, the inflammatory reactions induced nerve metamorphosis with a variety of neurotoxic factors including cytokines, chemokines, and reactive oxygen species. Thus, the activated microglia cell with various receptors (TSPO, COX, CR, P2XR, etc.) was perceived as important biomarkers for imaging the inflammatory progression. In this review, we would like to introduce the current status of the development of radiotracers that can image activated microglia.

Anti-neuroinflammatory Effects of a Locusta migratoria Ethanol Extract in LPS-stimulated BV-2 Microglia (LPS로 자극된 미세아교세포에서 풀무치 에탄올 추출물의 신경염증 억제 효능)

  • Lee, Hwa Jeong;Seo, Minchul;Lee, Joon Ha;Kim, In-Woo;Kim, Sun Young;Hwang, Jae-Sam;Kim, Mi-Ae
    • Journal of Life Science
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    • v.28 no.11
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    • pp.1332-1338
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    • 2018
  • Activated microglia, induced by various pathogens, protect neurons and maintain homeostasis of the central nervous system (CNS). However, severe activation causes neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease because of the secretion of various neurotoxic molecules, such as nitric oxide (NO), prostaglandin (PG), and pro-inflammatory cytokines. Because chronic microglial activation endangers neuronal survival, negative regulators of microglial activation have been identified as potential therapeutic candidates for treatment of many neurological diseases. One potential source of these regulators is Locusta migratoria, a grasshopper of the Acrididae, usually 4-6 cm in size, belonging to the family of large insects in Acrididae. This grasshopper is an edible insect resource that can be consumed by humans as protein source or used for animal feed. The aim of the present study was to examine the inhibitory effects of a L. migratoria ethanol extract (LME) on the production of inflammatory mediators in LPS-stimulated BV-2 microglia cells. The extract significantly inhibited the NO, iNOS, COX-2, and pro-inflammatory cytokine ($TNF-{\alpha}$, IL-6 and $IL-1{\beta}$) levels in BV-2 microglia cell. Because the inhibition of microglial activation may be an effective solution for treating brain disorders like Alzheimer's and Parkinson's diseases, these results suggest that LME may be a potential therapeutic agent for the treatment of brain disorders induced by neuroinflammation.

Effect of Cigarette Smoke Exposure Against Oxidative Damage in Scrapie-infected Mice

  • Sohn, Hyung-Ok;Moon, Ja-Young;Lim, Heung-Bin;Lee, Dong-Wook
    • Journal of the Korean Society of Tobacco Science
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    • v.31 no.1
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    • pp.29-38
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    • 2009
  • Although prion diseases, a group of fatal neurodegenerative diseases of human and animals, are presumed to be caused by several mechanisms including abnormal change of prion protein, oxidative stress is still believed to play a central role in development of the diseases. Cigarette smoking has a few beneficial effects on neuronal diseases such as Alzheimer's disease and Parkinson's disease despite of many detrimental effects. In this study, we investigated how chronic cigarette smoking could exert such beneficial effect against oxidative damage. For this study, homogenates of 87V scrapie-infected brain was inoculated on intracerebral system of IM mice through stereotaxic microinjection and biochemical properties concerning with oxidative stress were examined. The scrapie infection decreased the activity of mitochondrial Mn-containing superoxide dismutase by 50% of the control, meanwhile the effects on other antioxidant enzymes including Cu or Zn-containing superoxide dismutase were not significant. Additionally, the infection elevated superoxide level as well as monoamine oxide-B (MAO-B) in the infected brain. Interestingly, many of the detrimental effects were improved in partial or significantly by long-term cigarette smoke exposure (CSE). CSE not only completely prevented the generation of mitochondrial superoxide but also significantly (p<0.05) decreased the elevated mitochondrial MAO-B activity in the infected brain. Concomitantly, CSE prevented subsequent protein oxidation and lipid peroxidation caused by scrapie infection; however, it did not affect the activities of antioxidant enzymes. These results suggest that chronic exposure of cigarette smoke contribute to in part preventing the progress of neurodegeneration caused by scrapie infection.

The antioxidant activities of Korean Red Ginseng (Panax ginseng) and ginsenosides: A systemic review through in vivo and clinical trials

  • Park, Soo Kyung;Hyun, Sun Hee;In, Gyo;Park, Chae-Kyu;Kwak, Yi-Seong;Jang, Young-Jin;Kim, Bumseok;Kim, Jong-Hoon;Han, Chang-Kyun
    • Journal of Ginseng Research
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    • v.45 no.1
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    • pp.41-47
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    • 2021
  • A wide range of studies have steadily pointed out the relation of oxidative stress to the primary and secondary causes of human disease and aging. As such, there have been multiple misconceptions about oxidative stress. Most of reactive oxygen species (ROS) generated from chronic diseases cause oxidative damage to cell membrane lipids and proteins. ROS production is increased by abnormal stimulation inside and outside in the body, and even though ROS are generated in cells in response to abnormal metabolic processes such as disease, it does not mean that they directly contribute to the pathogenesis of a disease. Therefore, the focus of treatment should not be on ROS production itself but on the prevention and treatment of diseases linked to ROS production, including types 1 and 2 diabetes, cancer, heart disease, schizophrenia, Parkinson's disease, and Alzheimer's disease. In this regard, Korean Red Ginseng (KRG) has been traditionally utilized to help prevent and treat diseases such as diabetes, cancer, inflammation, nervous system diseases, cardiovascular disease, and hyperlipidemia. Therefore, this review was intended to summarize in vivo animal and human clinical studies on the antioxidant activities of KRG and its components, ginsenosides.

The oriental medical study about the arrythmia detected on the radial pulses and the result of ECG (촌관척(寸關尺)부의 검측한 부정맥과 electrocardiographic 결과와의 한의학적 검토)

  • Lyu, Heui-Yeong;Heo, Eun-Jung;Kim, Ji-Hyon;Yun, Jung-Mi;Jeon, Seong-Ha
    • Journal of the Korean Institute of Oriental Medical Informatics
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    • v.14 no.1
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    • pp.81-106
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    • 2008
  • The ECG which used for this paper, is analysis result from alogrisms of arrythmia, and we have studied that how we could certain Cold(寒 )type or Heat(熱) type and that Deficiency(虛) type or Excess(實)type of organs from various special diseases, and we obtained like these results. 1. we depend on our examination about Pulse(脈) because we can't discriminate arrythmia using EKG analysis instruments. 2. We obtained that Cold(寒) type diseases had wave that prolonged above normal baseline and ST wave which had downward aptitude. 3. We obtained that Heat(熱) type diseases had the fibrillation which had shortend wave that compare to normal and had downward aptitude or negative aptitude. 4. We obtained that Respiratory system (肺) diseases had wave that is within normal or is short of normal range and had much fluctuation in potential difference or trans on P wave. 5. The character of EKG which presented about diseases of gastric systems is prolonged above narmal range of wave, and the EKG had represented mixed wave with Heat(熱) type when accompany inflammatory in gastric system. 6. The wave of Blood Stasis(瘀血) type had upward aptitude of QRS wave, and the wave of anemia or blood loss type(少血 ) had downward aptitude of QRS wave, the wave which had both Cold(寒) and Heat (熱) represented mixed waves. 7. The Knotted Pulse(結脈) and Intermittent Pulse(代脈) is corresponded with sinus brady cardia, and the Swift Pulsle(疾脈) is corresponded with fibrillation. 8. We pay attention to the relations of formations about pressures pulse from formations of EMD( electromechanical dissociation ). From these results, we will have to study about EKG which using in tests of change of Parkinsons disease.

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Protective Effects of Hyperoside from Juglans sinensis Leaves against 1-methyl-4-phenylpyridinium-Induced Neurotoxicity (1-methyl-4-phenylpyridinium으로 유도된 신경 손상에 대한 호두나무잎에서 분리된 Hyperoside의 보호 효과)

  • Pariyar, Ramesh;Svay, Thida;Seo, Jungwon
    • Korean Journal of Pharmacognosy
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    • v.49 no.3
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    • pp.231-239
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    • 2018
  • Parkinson's disease (PD), one of common neurodegenerative diseases, is caused by the death of dopaminergic neurons in the substantia nigra pars compacta. The loss of dopaminergic neurons in PD is associated with oxidative stress and mitochondrial dysfunction. Hyperoside (quercetin 3-O-${\beta}$-D-galactopyranoside) was reported to have protective properties against oxidative stress by reducing intracellular reactive oxygen species (ROS) and increasing antioxidant enzyme activity. In this study, we examined the neuroprotective effect of hyperoside against 1-methyl-4-phenyl pyridinium ($MPP^+$)-induced cell model of PD and the underlying molecular mechanisms. Hyperoside significantly decreased $MPP^+$-induced cell death, accompanied by a reduction in poly ADP-ribose polymerase (PARP) cleavage. Furthermore, it attenuated $MPP^+$-induced intracellular ROS and disruption of mitochondrial membrane potential (MMP), with the reduction of Bax/Bcl-2 ratio. Moreover, hyperoside significantly increased the phosphorylation of Akt, but it has no effects on $GSK3{\beta}$ and MAPKs. Pharmacological inhibitor of PI3K/Akt abolished the cytoprotective effects of hyperoside against $MPP^+$. Taken together, these results demonstrate that hyperoside significantly attenuates $MPP^+$-induced neurotoxicity through PI3K/Akt signaling pathways in SH-SY5Y cells. Our findings suggest that hyperoside might be one of the potential candidates for the treatment of PD.