• 제목/요약/키워드: Fibril

검색결과 123건 처리시간 0.025초

End-to-end Structural Restriction of α-Synuclein and Its Influence on Amyloid Fibril Formation

  • Hong, Chul-Suk;Park, Jae Hyung;Choe, Young-Jun;Paik, Seung R.
    • Bulletin of the Korean Chemical Society
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    • 제35권12호
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    • pp.3542-3546
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    • 2014
  • Relationship between molecular freedom of amyloidogenic protein and its self-assembly into amyloid fibrils has been evaluated with ${\alpha}$-synuclein, an intrinsically unfolded protein related to Parkinson's disease, by restricting its structural plasticity through an end-to-end disulfide bond formation between two newly introduced cysteine residues on the N- and C-termini. Although the resulting circular form of ${\alpha}$-synuclein exhibited an impaired fibrillation propensity, the restriction did not completely block the protein's interactive core since co-incubation with wild-type ${\alpha}$-synuclein dramatically facilitated the fibrillation by producing distinctive forms of amyloid fibrils. The suppressed fibrillation propensity was instantly restored as the structural restriction was unleashed with ${\beta}$-mercaptoethanol. Conformational flexibility of the accreting amyloidogenic protein to pre-existing seeds has been demonstrated to be critical for fibrillar extension process by exerting structural adjustment to a complementary structure for the assembly.

Development of Inhibitors of $\beta$-Amyloid Plaque Formation

  • Kim, Dong-Jin
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 2006년도 Spring Conference
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    • pp.123-135
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    • 2006
  • Alzheimer's disease (AD) is the most common form of dementia in the aging population and is clinically characterized by a progressive loss of cognitive abilities. Pathologically, it is defined by the appearance of senile plaques - extracellular insoluble, congophilic protein aggregates composed of amyloid $\beta$ (A$\beta$) and neurofibrillary tangles (NFTs) - inyracellular lesions consisting of paired helical filaments from hyperphosphorylated cytoskeletal tau protein as described by Alois Alzheimer a century ago. These hallmarks still serve as the major criteria for a definite diagnosis of the disease. Consequently, one of the key strategy for drug development in this disease area focuses on reducing the concentration of cerebral A$\beta$ plaque by using substances that inhibit A$\beta$ fibril formation. We focused on developing inhibitors by synthesizing several kinds of aromatic molecules. The synthetic compounds were initially screened to evaluate the effective compound by tioflavin T fluorescence assay. The selected effective compounds were tested cytotoxicity and protective effect from A$\beta$-induced neuronal toxicity by cell based MTT assay with HT22 hippocampal neurons. The BBB permeability on effectors was also tested in in vitro co-culture model(HUVEC/C6 cell line). The behavior test wea carried out in mutant APP/PS1 transgenic mouse model of Alzheimer's disease. And inhibition of A$\beta$ fibril formation by the effective compound was monitored with transmitted electron microscopic images.

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Structural Properties of Fibril-forming Segments of α-Synuclein

  • Yoon, Je-Seong;Park, Joon-Ho;Jang, Soon-Min;Lee, Kyung-Hee;Shin, Seo-Min
    • Bulletin of the Korean Chemical Society
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    • 제30권3호
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    • pp.623-629
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    • 2009
  • We have performed replica-exchange molecular dynamics simulations on 41 residue peptide mainly composed of NAC (non A$\beta$ component) sequence in $\alpha$-Synuclein. To investigate conformational characteristics of intrinsically unstructured peptides, we carried out structural analysis on the ‘representative structures’ for ensemble of structures occurring at different temperatures. The secondary structure profile obtained from our simulations suggests that the NAC region of $\alpha$-synuclein can be divided into roughly three helical-like segments. It is found that the overall helix-turn-helix like topology is conserved even though the conformational fluctuations grow as the temperature increases. The coordinate-based and the distance-based representative structures exhibit noticeable differences at higher temperatures while they are similar at lower temperatures. It is found that structural variations for the coordinate-based representative structures are much larger, suggesting that distance-based representative structures provide more reliable information concerning characteristic features of intrinsically unstructured proteins. The present analysis also indicates that the conformational features of representative structures at high temperatures might be related to those in membrane or low pH environment.

악취가스 제거를 위안 섬유상 담체를 적용한 바이오필터 운전조건에 관한 연구 (Study of Operation Condition of Biofilter Using Fibril-form Matrix for Odor Gas Removal)

  • 정귀택;이광연;변기영;이경민;선우창신;이우태;박찬영;김도형;차진명;장영선;박돈희
    • KSBB Journal
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    • 제20권5호
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    • pp.341-344
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    • 2005
  • 섬유상 담체를 이용한 2단 소형 바이오필터를 이용한 악취가스 처리공정의 운전조건을 확립하기 위하여 BTX를 처리대상 물질로 바이오필터를 연속적으로 운전하여 섬유상 바이오필터 담체에 악취가스 처리용 미생물을 부착시킨 결과 우수한 부착된 생물막을 형성하여 높은 처리효율 $93\%$를 얻을 수 있었다. 또한, 악취 유입 농도 400 ppm 미만에서 체류시간 10 sec일 때 1단 반응기에서 $76\%$ 정도 제거율을 보이다가 2단 반응기에서 약 $93\%$의 제거율을 나타내었다. 그러나 체류시간이 15 sec 이상인 경우에는 제거효율이 $97\%$ 이상 유지되었다.

ON THE DISCREPANCY OF CORONAL MAGNETIC FIELDS IN SOLAR OPTICS AND RADIO

  • MA YUE-HuA;LI XIAO-QING
    • 천문학회지
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    • 제29권spc1호
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    • pp.309-311
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    • 1996
  • It is analysed the discrepancy about the coronal magnetic field between solar optic and solar radio using magnetic fibril concept with filling factor and fractal structure model. The magnetic field of $\~$ 100 G considered in solar optics is mean value in a large scale, and that of $\~$1000 G in solar should be the value of fine structures inside 'macro' loop.

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메타크릴아마이드 그라프트 중합견의 분석 방법 (Analyses for Identification of Methacrylamide Graft-Polymerized Silk)

  • 이용우
    • 한국잠사곤충학회지
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    • 제29권1호
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    • pp.64-68
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    • 1987
  • 견에 대한 비닐단량체의 증량가공에 있어서 메타크릴아마이드(metacrylamide) 크라프트 가공견의 판별 방법을 확립하기 위하여 가공견에 대한 정성분석과 미세구조를 관찰한 결과 가공견의 용해성 및 실소함유량은 미가공견에 비하여 저하되었으며 IR-Spectra도 파장 1385cm-1, 1210cm-1에서 미가공견과 다른 흡수 peak를 보였고 가공견의 pyrogram은 메타크릴아마이드의 세분해로 미가공견에서는 나타나지 않은 또 다른 peak를 보였다. 또한 가공견의 표면미세구조는 미가공견에 비하여 fibril이 팽대하여져 거친 면을 보였다.

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Synthesis of 6-[2-(Benzoxazol-2-ylmethylamino )ethoxy]-1-Alkyl­1 H-lndole-2-Carboxylic Acid and Inhibitory Activity on $\beta$-Amyloid Aggregation

  • Lee, Sun-Mi;Jeon, Raok
    • Archives of Pharmacal Research
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    • 제28권11호
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    • pp.1219-1223
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    • 2005
  • 6-[2-(Benzoxazol-2-ylmethylamino)ethoxy]-1-alkyl-1H-indole-2-carboxylic acids were designed and synthesized as $\beta$-amyloid (A$\beta$) fibril assembly inhibitors. Their inhibitory activity on A$\beta$, aggregation was evaluated by thioflavin T assay although their activities were insignificant.

게 껍질로부터 Microcrystalline Chitin 제조와 특성 규명 (Preparation and Characterization of Microcrystalline Chitin from Crab Shell)

  • 김성배
    • KSBB Journal
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    • 제11권4호
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    • pp.481-488
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    • 1996
  • Chitin 유도체의 다양한 응용성에도 불구하고 chi­tin의 강한 내약품성과 적당한 용매부재로 산업적인 용도개발은 매우 부진한 실정 이다. 이와 같은 chitin 의 강한 내약품성을 완화시키는 방법의 하나는 chi­tin을 가수분해하여 MCC를 제조동}는 것이다. 기존의 MCC 제조공정은 주로 강산을 사용하는 공정이어서 사용한 산을 제거하거나 회수하기 위해 많은 후처리가 필요하다. 그래서 이를 대체할 수 있는 공정으로 초음파와 과산화수소를 붉은 엽산과 함께 사용하는 공정을 개발하였다. 이 공정의 주요변수로는 산농도, 팽윤시간 및 온도 그리고 초음파 조사시간 및 주파수이고 이들 변수가 분자량에 미치는 영향을 조사하였다. MCC의 분자량은 chitin 분자량 크기의 약 1/8인 30,000 정도였고, 어떤 일정한 크기에 접 근해 가는 것을 발견하였다. 이와 같은 현상은 cellu lose의 분자배열모델을 도입하여 해석하였다. Chitin 과 MCC 모두 섬유형태로 되어 었으며, MCC의 fi bril 크기는 chitin의 fibril 크기보다 훨씬 작음을 알 수 있었다.

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End-terminal Capping 효과가 아밀로이드 섬유의 기계적 특성에 미치는 영향 연구 (End-Terminal Capping Effect on Mechanical Property of Transthyretin (TTR105-115) Amyloid Fibril)

  • 최현성;이명상;나성수
    • 대한기계학회논문집A
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    • 제41권7호
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    • pp.621-627
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    • 2017
  • 다양한 신경성 퇴행 질병을 유발하는 아밀로이드 섬유의 기계적 특징에 대한 이해는 아밀로이드 성장 메커니즘에 직접 관련되어 있기 때문에 질병 역학적 관점에서 많은 연구 진행 되어 왔다. 최근 아밀로이드 섬유의 높은 물성 값과 자가 결합능력을 통해 새로운 재료로 이용 하려는 시도가 진행되고 있다. 본 연구에서는 심혈관 질환을 유발하는 transthyretin($TTR_{105-115}$)의 핵심 영역의 기계적 특성을 분자 동역학 전산 역학을 통해 평가했다. 특히 end-terminal capping의 효과가 $TTR_{105-115}$의 구조적 안정성에 미치는 영향을 평가했다. 인장모사 분자 동역학을 통해(steered molecular dynamics, SMD) 기계적 거동과 물성을 측정하였다. 재료의 기계적 특성에 영향을 주는 인자를 밝히고 자연 모사 재료로써의 활용 가능성에 대한 제시를 하였다.

염산테트라싸이클린을 이용한 치근면처리의 효과 (Effect of Tetracycline-HCL in Root Conditioning;A SEM Study)

  • 김은정;허익;이만섭;권영혁
    • Journal of Periodontal and Implant Science
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    • 제30권1호
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    • pp.121-134
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    • 2000
  • Root conditioning has introduced to dissolve the smear layer and to produce surface demineralization, resulting to exposure of dentin collagen fibril and opening of dentinal tubules. The purpose of the present study was to examine the effect of different concentration and application time of tetracycline-HCL on root conditioning. Total 40 root specimen were prepared from 20 periodontitis-prone human single rooted tooth. The specimen were treated with tetracycline-HCL solution(20mg/ml, 50mg/ml, 100mg/ml)for 20 sec, 3 min, 5 min., and saline for 30 sec. The application method was rubbing method with cotton pellet. Under the scanning electron microscopy(20KV), the extent of smear removal and opening of the dentinal tubules were examined at x 3000. The following results were obtained. 1. Treatment of root specimen with saline did not remove the smear layer and open the dentinal tubules. 2. Treatment of root specimen with different concentration of tetracycline-HCL for 20 sec also did not remove the smear layer completely. 3. Treatment of root specimen with different concentration of tetracycline-HCL for 3 min opened the dentinal tubules and removed smear layer. 4. Treatment of root specimen with 50mg/ml of tetracycline-HCL for 3 min showed collagen fibril within the opened dentinal tubules. In conclusion, the effect of root conditioning with tetracycline-HCL is more dependent on the application time than the application concentration. Root conditioning with 50mg/ml tetracycline-HCL for 3 min is enough for obtaining the periodontal regeneration.

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