• Title/Summary/Keyword: tau 단백질

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Cloning and Experssion of a Human tau Gene cDNA in Escherichia coli (인체 tau 유전자의 cDNA 클로닝 및 Escherichia coli에서의 발현)

  • Chung, Sang-Ho;Maeda, Tadakazu;Yanagawa, Hiroshi
    • Korean Journal of Microbiology
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    • v.32 no.1
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    • pp.28-33
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    • 1994
  • In normal cells tau protein is associated with axonal microtubules, whereas in Alxheimer's disease it is immobilized in the somatodendritic compartment of certain nerve cells as a major component of the paired helical filament. As a part of the study to analyze the nature of the paired helical filament (PHF) deposits and some related factors in brain, we have cloned and expressed a human tau gene cDNA in Escherichia coli to obtain the recombinant human tau protein in abundance.

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Clinical and Pathological Characteristics of Frontotemporal Lobar Degeneration(FTLD) and Molecular Genetics of Tau Protein (Frontotemporal Lobar Degeneration(FTLD)의 임상적, 병리적 특징과 타우 단백질의 분자 유전학)

  • Woo, Sung-Il
    • Korean Journal of Biological Psychiatry
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    • v.10 no.2
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    • pp.97-106
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    • 2003
  • Criticisms about amyloid cascade hypothesis of Alzheimer's disease(AD) are based on the findings, first, that the degree of dementia does not correlate with the number of plaques, and second, that the neurofibrillary tangle formation seems to predate plaque formation. In addition, neurofibrillary tangle counts correlate well with the degree of cognitive impairment. These findings suggest the independent importance of tau abnormality in AD research which is involved in the neurofibrillary tangle formation. Recently, tau pathology without amyloid deposits and mutations in tau protein gene were reported to be the major pathogenic mechanism in Pick's disease, progressive supranuclear palsy, corticobasal degeneration and FTDP-17(frontotemporal dementia and parkinsonism linked with chromosome 17). These data suggest that understanding the causes and consequences of tau dysfunction might give new clinical and therapeutic solutions to many known tauopathies.

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Neurobiology of Alzheimer's Disease (알쯔하이머 질환의 신경생물학)

  • Chung, Young-Cho;Seo, Seung-Woo;Lee, Seung-Hwan
    • Korean Journal of Biological Psychiatry
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    • v.8 no.1
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    • pp.62-70
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    • 2001
  • Alzheimer's disease(AD) is associated with a characteristic neuropathology. The major hallmarks of AD are senile plaques (SPs) and neurofibrillary tangles(NFTs). ${\beta}$-amyloid protein($A{\beta}$) is derived from the proteolysis of amyloid precursor protein(APP) and then converted to SPs. Mature SPs produce cytotoxicity through direct toxic effects and activation of microglia and complement. NFTs are composed of paired helical filaments(PHFs) including abnormally phosphorylated form of the microtubule-associated protein(MAP) tau and increased tau level in cerebrospinal fluid may be observed in most AD. The aggregation of $A{\beta}$ and tau formation are thought to be a final common pathway of AD. Acetylcholine, dopamine, serotonin, GABA and their receptors are associated with AD. Especially, decreased nicotinic acetylcholine receptors(nAChRs) in AD are reported. Genetic lesions associated with AD are mutations in the structural genes for the APP located on chromosome 21, presenilin(PSN)1 located on chromosome 14 and PSN2 located on chromosome 1. Also, trisomy 21, Apo-E gene located on chromosome 19, PMF locus, low density lipoprotein receptor-related protein and ${\alpha}$-macroglobulin increase risk of AD. In this article, we will review about the neurobiology of AD and some newly developed research areas.

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Cerebrolysin Attenuates Astrocyte Activation Following Repetitive Mild Traumatic Brain Injury: Implications for Chronic Traumatic Encephalopathy (만성외상성뇌병증과 관련된 반복적 경도 외상성뇌손상(rmTBI)모델에서 cerebrolysin의 별아교 세포활성 억제효과)

  • Kang, Hyun Bae;Kim, GiHun;Kim, HyunJoong;Han, Sa Rang;Chae, Dong Jin;Song, Hee-Jung;Kim, Dong Woon
    • Journal of Life Science
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    • v.23 no.9
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    • pp.1096-1103
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    • 2013
  • Chronic traumatic encephalopathy (CTE), which is common in athletes, is a progressive neurodegenerative disease and a long-term consequence of repetitive closed head injuries. CTE is regarded as a chronic brain syndrome due to the effects of repetitive traumatic brain injury (TBI). Because neurotrophic factors are neuroprotective in models of brain and spinal cord injuries, we examined the effects of cerebrolysin, a mixture of various neurotrophic factors, on brain pathology in a mouse model of repetitive mild TBI (rmTBI), which is a good model of CTE. Five groups were created and treated as follows: groups 1 and 2: rmTBI for 4 weeks following cerebrolysin injection for 4 weeks; groups 3 and 4: rmTBI for 8 weeks with or without cerebrolysin injection for 4 weeks; group 5: control. We found that p-tau expression was increased in the pyramidal layer of the cortex and hippocampus, particularly the CA3 region, but not in the CA1 region and the dentate gyrus (DG). Intra-tail vein administration of cerebrolysin ($10{\mu}l$ of 1 mg/ml) after/during rmTBI treatment reduced p-tau expression in both the cortex and hippocampus. Histological analysis revealed mild astrocyte activation (increased expression of glial fibrillary acidic protein (GFAP)) but not microglia activation (ionized calcium binding adaptor molecule 1 (iba-1) expression) and peripheral macrophage infiltration (CD45). Additionally, administration of cerebrolysin after rmTBI resulted in reduced astrocyte activation. These observations in rmTBI demonstrated that cerebrolysin treatment reduces phosphorylation of tau and astrocyte activation, attenuates brain pathology, and mitigates function deficits in TBI. Taken together, our observations suggest that cerebrolysin has potential therapeutic value in CTE.

Recent Updates on PET Imaging in Neurodegenerative Diseases (퇴행성 뇌질환에서 PET의 발전과 임상적 적용 및 최신 동향)

  • Yu Kyeong Kim
    • Journal of the Korean Society of Radiology
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    • v.83 no.3
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    • pp.453-472
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    • 2022
  • Over the past decades, the immense clinical need for early detection methods and treatments for dementia has become a priority worldwide. The advances in PET biomarkers play increasingly important roles in understanding disease mechanisms by demonstrating the protein pathology underlying dementia in the brain. Amyloid-β and tau deposition in PET images are now key diagnostic biomarkers for the Alzheimer's disease continuum. The inclusion of biomarkers in the diagnostic criteria has achieved a paradigm shift in facilitating early differential diagnosis, predicting disease prognosis, and influencing clinical management. Furthermore, in vivo images showing pathology could become prognostic as well as surrogate biomarkers in therapeutic trials. In this review, we focus on recent developments in radiotracers for amyloid-β and tau PET imaging in Alzheimer's disease and other neurodegenerative diseases. Further, we introduce their potential application as future perspectives.

Therapeutic Effect of the Mixed Extract of Panax ginseng C.A. Mey. and Chaenomeles sinensis Koehne on the Injury of Brain Tissue in the Mice by Alzheimer's Disease (Alzheimer성 치매 유발 생쥐의 뇌조직 손상에 대한 인삼, 목과 혼합추출액의 치료 효과)

  • Han, Sin-Hee;Doh, Eun-Soo
    • Korean Journal of Plant Resources
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    • v.20 no.4
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    • pp.325-330
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    • 2007
  • This study was conducted to investigate the effect of the mixed extract of P. ginseng C.A. Mey. and C. sinensis K. (Gin-CHF) on the infarction area of hippocampus in the mice with Alzheimer's disease induced by ${\beta}-amyloid({\beta}A)$. The Gin-CHF extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. The Gin-CHF extract reduced the Tau protein, GFAP protein, and presenilin1/presenilin2 protein (immunohistochemistry) of hippocampus in the mice with Alzheimer's disease induced by ${\beta}A$. These results suggest that the Gin-CHF extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the Gin-CHF extract for Alzheimer's disease is suggested for further research.

Potential Involvement of p62, a Phosphotyrosine-independent Ligand of SH2 Domain of $p56^{lck}$, on UV-induced Apoptosis in Jurkat T-cell Line ($p56^{lck}$ SH2 domain 결합 단백질 p62가 Jurkat T-세포주의 세포예정사에 미치는 영향)

  • 정인실
    • Development and Reproduction
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    • v.2 no.2
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    • pp.165-171
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    • 1998
  • p62 is a novel cytoplsmic protein that binds to SH2 domain of p56$^{lck}$, lymphocyte-specific protein tyrosine kinase, and the expression of p62 was observed in most tissues. In addition p62 interacts with various proteins including ubiquitin and atypical PKC isoform, indicating its diverse biological role in different tissues. However, little is known about functional connection between p62 and its binding proteins. In the present study, a novel cellular protein, p62 has been shown to bind to 14-3-3 $\tau$ isoform that is specific for T cells. Moreover, overexpression of p62 in T cells caused to delay onset of UV-induced apoptosis characterized by DNA fragmentation and breakdown of poly (ADP-ribose) polymerase (PARP). Lately, 14-3-3 proteins have been shown to mediate survival signal via interacting proapoptotic Bad protein in the Iymphocyte. These results suggested the presence of p62-mediated regulatory mechanism during apoptosis in T cells, in which activation-induced apoptotic signal could be interfered by p62 and 14-3-3 protein.n.

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Alzheimer Dementia and Microvascular Pathology: Blood-Brain Barrier Permeability Imaging (알츠하이머 치매와 미세뇌혈관병리: 혈액뇌장벽 투과도 영상)

  • Won-Jin Moon
    • Journal of the Korean Society of Radiology
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    • v.81 no.3
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    • pp.488-500
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    • 2020
  • Accumulating evidence suggests that Alzheimer's disease (AD) is not only caused by accumulation of abnormal proteins, including amyloid and tau, but is also closely associated with abnormalities in the microvascular environment including the blood-brain barrier (BBB), both of which lead to neuroinflammation and neurodegeneration. Application of in vivo magnetic resonance imaging (MRI) has recently increased to assess BBB permeability in AD and related diseases. Here, we provide a narrative review of BBB permeability-related pathology in Alzheimer dementia and recent MRI research on BBB permeability changes in AD and related diseases. Furthermore, we briefly introduce the measurement of BBB permeability using MRI and its methodological issues.

Effects of Body Weight and Dietary Protein Level on Ammonia Excretion by the Nile tilapia Oreochromis niloticus (나일틸라피아의 암모니아 배설에 미치는 어체중과 사료 내 단백질 함량의 영향)

  • Oh, Sung-Yong;Jo, Jae-Yoon
    • Journal of Aquaculture
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    • v.18 no.2
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    • pp.122-129
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    • 2005
  • Ammonia is the major limiting factor in intensive aquaculture production systems. Therefore, quantification of ammonia excretion is important for the water quality management in aquaculture systems. Ammonia excretion is known to be affected by many factors such as body weight and dietary protein level (DPL). In this study, experiments were carried out to investigate the effects of body weight and DPLs on the rates of ammonia excretion of Nile tilapia Oreochromis niloticus. Three sizes of fishes (mean initial weight; 4.8 g,42.7 g and 176.8 g) were fed each of two dietary protein levels (30.5% and 35.5%). Daily feeding levels for the three fish sizes of 4.8 g, 42.7 g and 176.8 g were 6%, 3%, and 1.5% body weight per day, respectively. Each group of fish was stocked in a 17.1-L aquarium and all treatments were triplicated. Following feeding, the weight-specific ammonia excretion rate of O. niloticus increased, peaked at 4 to 8 h, and returned to pre-feeding levels within 24 h. Total ammonia nitrogen (TAN) excretion.ate per unit weight decreased with the increase of fish weight for each diet (P<0.05). The TAN excretion rate increased with increasing dietary protein content for each fish size (P<0.05). TAN excretion rates (Y) for each diet with different fish weights were described by the following equations: low DPL diet (30.5%): $Y\;(mg\;kg^{-1}\;d^{-1})=955.69-147.12\;lnX\;(r^2=0.95)$, high DPL diet (35.5%): $Y\;(mg\;kg^{-1}\;d^{-1})=1362.41-209.79\;lnX\;(r^2=0.99)$. Where: X=body weight (g wet wt.). The TAN excretion rates ranged 28.5%-37.1% of the total nitrogen ingested for the low DPL diet (30.5%) and 37.4-38.5% for the high DPL diet (35.5%). Total nitrogen losses of fish fed the high DPL diet $(35.5%;\;0.26\sim0.91g\;kg^{-1}\;d^{-1})$ were higher than those fed the low DPL diet $(30.5%;\;0.22\sim0.68g\;kg^{-1}\;d^{-1})$. The losses decreased per kg of fish as fish size increased. Results will provide valuable information fer water quality management and culture of Nile tilapia in recirculating aquaculture systems.

Development of Fluorescent Small Molecules for Imaging of Alzheimer's Disease Biomarkers (알츠하이머병의 영상 진단을 위한 형광 프로브의 개발)

  • Min, Changho;Ha, Heonsu;Jeon, Jongho
    • Applied Chemistry for Engineering
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    • v.32 no.1
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    • pp.1-9
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    • 2021
  • Alzheimer's disease (AD), an irreversible degenerative disorder, is associated with accumulation and aggregation of amyloid-β peptides, hyperphosphorylated tau proteins, and high level of metal ions in the brain. Up to date, there is no effective therapeutic agent to stop the progress of the disease and thus early and accurate diagnosis of AD has gained increasing attention in recent years. Among several diagnostic methods, an optical imaging using fluorescent probes is one of the most promising tools to visualize AD biomarkers. In this review, we will introduce fluorescent probes that can be applied to in vivo brain imaging of AD models and also their structure. It is expected that the present review will provide useful information to many scientists in the related research fields.