• 제목/요약/키워드: Neurodegenerative disease

검색결과 494건 처리시간 0.021초

A New Mathematical Model for Optimum Production of Neural Stem Cells in Large-scale

  • Hossain, S.M. Zakir;Sultana, Nahid;Babar, S.M. Enayetul;Haki, G.D.
    • Molecular & Cellular Toxicology
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    • 제3권2호
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    • pp.77-84
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    • 2007
  • Millions of individuals worldwide are currently afflicted with neurodegenerative disorders such as Parkinson's disease and multiple sclerosis which are caused by the death of specific types of specialized cells in the Central Nervous System (CNS). Recently, Neural Stem Cells (NSCs) are able to replace these dead cells with new functional cells, thereby providing a cure for devastating neural diseases. The clinical use of neural stem cells (NSCs) for the treatment of neurological diseases requires overcoming the scarcity of the initial in vivo NSC population. Thus, we developed a novel 3-dimentional cellular automata model for optimum production of neural stem cells and their derivatives in large scale to treat neurodegenerative disorder patients.

Polyglutamine Residues from Machado-Joseph Disease Gene Enhance Formation of Aggregates of GST-Polyglutamine Fusion Protein in E. coli

  • Rhim, Hyang-Shuk;Bok, Kyoung-Sook;Chang, Mi-Jeong;Kim, In-Kyung;Park, Sung-Sup;Kang, Seong-Man
    • Journal of Microbiology and Biotechnology
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    • 제8권6호
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    • pp.663-668
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    • 1998
  • Several neurodegenerative diseases such as Huntington's disease, dentatorubralpallidoluysian atrophy, spinobulbar muscular atrophy, Machado-Joseph disease, and spinocerebellar ataxias type 1 are associated with the aggregation of expanded glutamine repeats within their proteins. Generally, in clinically affected individuals, the expansion of the polyglutamine sequences is beyond 40 residues. To address the length of polyglutamine that forms aggregation, we have constructed plasmids encoding glutathione S-transferase (GST) Machado-Joseph disease gene fusion proteins containing polyglutamine and investigated the formation of aggregates in E. coli. Surprisingly, even $(Gin)_8$, in the normal range as well as $(Gin)_{65}$ in the pathogenic range enhanced the formation of insoluble protein aggregates, whereas $(Ser)_8$, and $(Aia)_8$, did not form aggregates. Our results indicate that the formation of protein aggregates in GST-polyglutamine proteins is specifically mediated by the polyglutamine repeat sequence within their protein structure. Our study may contribute to the understanding of the molecular mechanism of the formation of protein aggregates in neurodegenerative disorders and the development of preventative strategies.

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Hippocampus Segmentation and Classification in Alzheimer's Disease and Mild Cognitive Impairment Applied on MR Images

  • Madusanka, Nuwan;Choi, Yu Yong;Choi, Kyu Yeong;Lee, Kun Ho;Choi, Heung-Kook
    • 한국멀티미디어학회논문지
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    • 제20권2호
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    • pp.205-215
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    • 2017
  • The brain magnetic resonance images (MRI) is an important imaging biomarker in Alzheimer's disease (AD) as the cerebral atrophy has been shown to strongly associate with cognitive symptoms. The decrease of volume estimates in different structures of the medial temporal lobe related to memory correlates with the decline of cognitive functions in neurodegenerative diseases. During the past decades several methods have been developed for quantifying the disease related atrophy of hippocampus from MRI. Special effort has been dedicated to separate AD and mild cognitive impairment (MCI) related modifications from normal aging for the purpose of early detection and prediction. We trained a multi-class support vector machine (SVM) with probabilistic outputs on a sample (n = 58) of 20 normal controls (NC), 19 individuals with MCI, and 19 individuals with AD. The model was then applied to the cross-validation of same data set which no labels were known and the predictions. This study presents data on the association between MRI quantitative parameters of hippocampus and its quantitative structural changes examination use on the classification of the diseases.

Flavonoids as anti-inflammatory and neuroprotective agents

  • Lee, Heesu;Selvaraj, Baskar;Yoo, Ki Yeon;Ko, Seong-Hee
    • International Journal of Oral Biology
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    • 제45권2호
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    • pp.33-41
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    • 2020
  • Neuroinflammation is known as the main mechanism implicated in the advancement of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The main feature of neuroinflammation is associated with the activation of microglia. The activated microglia increase proinflammatory cytokine production and induce progressive neuronal cell death. Citrus flavonoids show neuroprotective effects that are associated with the anti-inflammatory action of flavonoids in neurodegenerative diseases. Among these citrus flavonoids, kaempferol, naringin, and nobiletin show inhibitory effects on nuclear factor-κB and mitogen-activated protein kinase signaling pathways that can modulate inflammatory conditions in microglial cells. In the present review, we present the anti-inflammatory activities of citrus flavonoids and therapeutic potential of flavonoids as neuroprotective agents.

Manganese and Iron Interaction: a Mechanism of Manganese-Induced Parkinsonism

  • Zheng, Wei
    • 한국환경성돌연변이발암원학회지
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    • 제23권4호
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    • pp.115-130
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    • 2003
  • Idiopathic Parkinson's disease (IPD) represents a common neurodegenerative disorder. While epidemiological studies have suggested a number of risk factors including age, gender, race, and inherited disorder, the cumulative evidence supports the view that environmental or occupational exposure to certain chemicals may contribute to the initiation and progress of Parkinsonism. More recently, clinical and laboratory investigations have led to the theory that dysregulation of iron, an essential metal to body function, may underlie IPD by initiating free radical reaction, diminishing the mitochondrial energy production, and provoking the oxidative cytotoxicity. The participation of iron in neuronal cell death is especially intriguing in that iron acquisition and regulation in brain are highly conservative and thus vulnerable to interference from other metals that bear the similar chemical reactivity. Manganese neurotoxicity, induced possibly by altering iron homeostasis, is such an example. In fact, the current interest in manganese neurotoxicology stems from two primary concerns: its clinical symptoms that resemble Parkinson's disease and its increased use as an antiknock agent to replace lead in gasoline. This article will commence with addressing the current understanding of iron-associated neurodegenerative damage. The major focus will then be devoted to the mechanism whereby manganese alters iron homeostasis in brain.

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ESCRT, autophagy, and frontotemporal dementia

  • Lee, Jin-A;Gao, Fen-Biao
    • BMB Reports
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    • 제41권12호
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    • pp.827-832
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    • 2008
  • Many age-dependent neurodegenerative diseases are associated with the accumulation of abnormally folded proteins within neurons. One of the major proteolytic pathways in the cell is the autophagy pathway, which targets cytoplasmic contents and organelles to the lysosomes for bulk degradation under various physiological and stressful conditions. Although the importance of autophagy in cellular physiology is well appreciated, its precise roles in neurodegeneration remain largely unclear. Recent studies indicate that components of the endosomal sorting complex required for transport (ESCRT) are important in the autophagy pathway. Reduced activity of some ESCRT subunits leads to the accumulation of autophagosomes and failure to clear intracellular protein aggregates. Interestingly, rare mutations in CHMP2B, an ESCRT-III subunit, are associated with frontotemporal dementia linked to chromosome 3 (FTD3). Mutant CHMP2B proteins seem to disrupt the fusion of autophagosomes and lysosomes in cell culture models. These findings suggest a potential mechanism for the pathogenesis of FTD3 and possibly other neurodegenerative diseases as well.

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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    • 제43권3호
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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.

Polyubiquitin-Proteasomal Degradation of Leucine-Rich Repeat Kinase 2 Wildtype and G2019S

  • Park, Sangwook
    • 대한의생명과학회지
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    • 제27권3호
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    • pp.182-186
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    • 2021
  • Parkinson disease (PD) is becoming one of the most neurodegenerative disorder worldwide. The deposited aggregates have been connected in the pathophysiology of PD, which are degraded either by ubiquitin-proteasomal system (UPS) or autophagy-lysosomal pathway (ALP). Leucin-rich repeat kinase 2 (LRRK2), one of the neurodegenerative proteins of PD is also stringently controlled by both UPS and ALP degradation as well. However, the polyubiquitination pattern of LRRK2 aggregates is largely unknown. Here, we found that K63-linked polyubiquitinations of G2019S mutant, most familial variant for PD, is highly enhanced compared to those of wild type LRRK2 (WT). In addition, in the presence of overexpressed p62/SQSTM-1, ubiquitination of LRRK2 WT or D1994A was reduced, whereas G2019S mutant was not diminished significantly. Therefore, we propose that degradation of G2019S via UPS is more involved with K63-linked ubiquitination than K48-linked ubiquitination, and overexpressed p62/SQSTM-1 does not enhance degradative effect on G2019S variant.

Advances and Applications of Mass Spectrometry Imaging in Neuroscience: An Overview

  • Bharath S. Kumar
    • Mass Spectrometry Letters
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    • 제14권3호
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    • pp.57-78
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    • 2023
  • Understanding the chemical composition of the brain helps researchers comprehend various neurological processes effectively. Understanding of the fundamental pathological processes that underpin many neurodegenerative disorders has recently advanced thanks to the advent of innovative bioanalytical techniques that allow high sensitivity and specificity with chemical imaging at high resolution in tissues and cells. Mass spectrometry imaging [MSI] has become more common in biomedical research to map the spatial distribution of biomolecules in situ. The technique enables complete and untargeted delineation of the in-situ distribution characteristics of proteins, metabolites, lipids, and peptides. MSI's superior molecular specificity gives it a significant edge over traditional histochemical methods. Recent years have seen a significant increase in MSI, which is capable of simultaneously mapping the distribution of thousands of biomolecules in the tissue specimen at a high resolution and is otherwise beyond the scope of other molecular imaging techniques. This review aims to acquaint the reader with the MSI experimental workflow, significant recent advancements, and implementations of MSI techniques in visualizing the anatomical distribution of neurochemicals in the human brain in relation to various neurogenerative diseases.

도파민 유도성 SH-SY5Y 세포독성에 대한 원지의 방어기전 연구 (Protective Effects of Radix Polygalae on Dopamine-induced Cell Death in Human SH-SY5Y Dopaminergic Neuroblastoma Cells)

  • 이지용;박재현;김경렬;김태헌;강형원;류영수
    • 동의생리병리학회지
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    • 제18권2호
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    • pp.544-552
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    • 2004
  • In oriental medicine, Radix Polygalae(RP) has been to treat tremors et al. But the mechanism how to decrease tremors was not known. The purpose of this study was to investigate the effect of RP on neurodegenerative disease. We used RP to execute the study of this defense mechanism on dopamine-induced cell death in human SH-SY5Y dopaminergic neuroblastoma cells. MTT assay was used to know the cytotoxicity of dopamine and the defense mechanism. As a result of this experiment, dopamine had cytotoxicity in human SH-SY5Y cells, but when it treated with RP, the cell survival rate increased. This suppressed the cell apoptosis, activation of caspase-3 protease, production of ROS, and repair of membrane potential change. In conclusion, RP has the protective effect on dopamine-induced cell death in human SH-SY5Y dopaminergic neuroblastoma cells, so this could be an effective agent on the neurodegenerative disease like Parkinsonism.