• 통합자연과학논문집
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• 제7권2호
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• pp.79-86
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• 2014

Amyloid oligomers are believed to play important causal roles in many types of amyloid-related degenerative diseases. Many different laboratories have reported amyloid oligomers that differ in size, morphology, toxicity, and method of preparation or purification, raising the question of the structural relationships among these oligomer preparations. The structural plasticity that has been reported to occur in amyloid formed from the same protein sequence indicates that it is quite possible that different oligomer preparations may represent distinct structural variants. In view of the difficulty in determining the precise structure of amyloids, conformation- and epitope-specific antibodies may provide a facile means of classifying amyloid oligomer structures. Conformation-dependent antibodies that recognize generic epitopes that are specifically associated with distinct aggregation states of many different amyloid-forming sequences indicate that there are at least two fundamentally distinct types of amyloid oligomers: fibrillar and prefibrillar oligomers. Classification of amyloid oligomers according to their underlying structures may be a more useful and rational approach than relying on differences in size and morphology.

• Nuclear Medicine and Molecular Imaging
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• 제41권2호
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• pp.112-117
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• 2007

Imaging distribution of ${\beta}-amyloid$ plaques in Alzheimer's disease is very important for early and accurate diagnosis. Early trial of the ${\beta}-amyloid$ plaques includes using radiolabeled peptides which can be only applied for peripheral ${\beta}-amyloid$ plaques due to limited penetration through the blood brain barrier (BBB). Congo red or Chrysamine G derivatives were labeled with Tc-99m for imaging ${\beta}-amyloid$ plaques of Alzheimer patient's brain without success due to problem with BBB penetration. Thioflavin T derivatives gave breakthrough for ${\beta}-amyloid$ imaging in vivo, and a benzothiazole derivative [C-11]6-OH-BTA-1 brought a great success. Many other benzothiazole, benzoxazole, benzofuran, imidazopyridine, and styrylbenzene derivatives have been labeled with F-18 and I-123 to improve the imaging quality. However, [C-11]6-OH-BTA-1 still remains as the best. However, short half-life of C-11 is a limitation of wide distribution of this agent. So, it is still required to develop an Tc-99m, F-18 or I-123 labeled agent for ${\beta}-amyloid$ imaging agent.

• Multiscale and Multiphysics Mechanics
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• 제1권1호
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• pp.53-64
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• 2016

Amyloid fibrils have recently been considered as an interesting material, since they exhibit the excellent mechanical properties such as elastic modulus in the order of 10 GPa, which is larger than that of other protein materials. Despite recent findings of these excellent mechanical properties for amyloid fibrils, it has not been fully understood how these excellent mechanical properties are achieved. In this work, we have studied the nanomechanical deformation behaviors and properties of amyloid fibrils such as their elastic modulus as well as fracture strength, by using atomistic simulations, particularly steered molecular dynamics simulations. Our simulation results suggest the important role of the length of amyloid fibrils in their mechanical properties such that the fracture force of amyloid fibril is increased when the fibril length decreases. This length scale effect is attributed to the rupture mechanisms of hydrogen bonds that sustain the fibril structure. Moreover, we have investigated the effect of boundary condition on the nanomechanical deformation mechanisms of amyloid fibrils. It is found that the fracture force is critically affected by boundary condition. Our study highlights the crucial role of both fibril length and boundary condition in the nanomechanical properties of amyloid fibrils.

• Bulletin of the Korean Chemical Society
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• 제24권9호
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• pp.1403-1406
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• 2003

• 대한세포병리학회지
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• 제4권2호
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• pp.121-126
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• 1993

Amyloid tumor is a tumorlike localized deposit of amyloid which is encountered occasionally in association with multiple myeloma and various chronic inflammatory diseases. This report describes a case of solitary amyloid tumor of the neck which was the presenting symptom arising in association with multiple myeloma. A 56-year-old woman complained of a palpable neck mass and fine needle aspiration was done. Multiple myeloma was diagnosed on the basis of the bone marrow biopsy and monoclonality of kappa light chain. The histologic and cytologic features of the amyloid appear to be characteristic and may allow a definitive diagnosis to be made on needle aspiration biopsy.

• 동의생리병리학회지
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• 제21권1호
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• pp.190-198
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• 2007

Alzheimer's disease, a representative neurodegenerative disorder, is characterized by the presence of senile plaques and neurofibrillary tangles accompanied by neuronal damages. b-Amyloid peptide is considered to be responsible for the formation of senile plagues that accumulate in the brains of patients with Alzheimer's disease. There has been compelling evidence supporting that b-amyloid-induced cytotoxicity is mediated through generation of reactive oxygen species. In this study, we have investigated the possible protective effect of Rehmannia glutihosaagainst b-amyloid-induced oxidative ceil death in cultured human neuroblastoma SH-SY5Y cells. SH-SY5Y cells treated with b-amyloid underwent apoptotic death as determined by morphological features and positive in situterminal end-labeling (TUNEL staining). Rehmannia glutinosawater extract, wine, and vinegar pretreatments attenuated b-amyloid-induced cytotoxicity and apoptosis. Rehmannia glutinosa vinegar exhibited maximum protective effect by increasing the expression of anti-apoptotic protein, Bcl-2. in addition to oxidative stress, b-amyloid-treatment caused nitrosative stress via marked increase in the levels of nitric oxide, which was effectively blocked by Rehmannia glutinosa. To further explore the possible molecular mechanisms underlying the protective effect of Rehmannia glutinosa, we assessed the mRNA expression of cellular antioxidant enzymes. Treatment of Rehmannia glutinosa vinegar led to up-regulation of heme oxygemase-1 and catalase. These results suggest that Rehmannia glutinosa could modulate oxidative neuronal cell death caused by b-amyloid and may have preventive or therapeutic potential in the management of Alzheimer's disease. Particularly, Rehmannia glutinosa vinegar can augment cellular antioxidant capacity, there by exhibiting higher neuroprotective potential.

• 농업과학연구
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• 제13권1호
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• pp.139-146
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• 1986

과망간산카리움법(法)을 이용(利用)하여 자연발생(自然發生)아밀로이드증(症)의 소(15례(例)), 개(1례(例)), 및 고양이 (1례(例)) 그리고 인공유발(人工誘發)아밀로이드증(症) (토끼, 1례(例))으로부터 채취(採取)한 아밀로이드단백(蛋白)의 침착장기(沈着臟器)에 대하여 침착(沈着)아밀로이드의 성상(性狀)을 조직화학적(組織化學的)으로 검사(檢査)하였다. 그 결과(結果), 소, 개 및 인공유발 토끼의 아밀로이드증(症)에서 각(各) 장기(臟器) 모두 적갈색(赤褐色)의 형광(螢光)및 녹색(綠色)의 편광(扁光)이 소실(消失)되어 과망간산카리움의 처리(處理)에 대해 감수성(感受性)이었다. 이 사실(事實)로 보아 소, 개 및 인공유발아밀로이드증례(症例) 모두 amyloid protein A(AA 단백(蛋白))에 상당(相當)하는 것으로 판명(判明)되었다. 반면 고양이 1증례(症例)에서는 과망간산카리움처리(處理) 후(後)에도 침착(沈着)아밀로이드의 Congo red에 대한 친화성(親和性)이 잔존(殘存)하였고 또한 신장(腎臟)의 사구체(絲球體)에 면역(免疫) 글리부린의 침착(沈着)이 인정(認定)된 점으로 보아, 본(本) 증례(症例)의 아밀로이드 단백(蛋白)은 amyloid light chain related protein (AL 단백(蛋白))에 상당(相當)하는 것으로 사료(思料)되었다.

• BMB Reports
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• 제48권1호
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• pp.13-18
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• 2015

Alzheimer's disease severely compromises cognitive function. One of the mechanisms to explain the pathology of Alzheimer's disease has been the hypotheses of amyloid-pore/channel formation by complex $A{\beta}$-aggregates. Clinical studies suggested the moderate alcohol consumption can reduces probability developing neurodegenerative pathologies. A recent report explored the ability of ethanol to disrupt the generation of complex $A{\beta}$ in vitro and reduce the toxicity in two cell lines. Molecular dynamics simulations were applied to understand how ethanol blocks the aggregation of amyloid. On the other hand, the in silico modeling showed ethanol effect over the dynamics assembling for complex $A{\beta}$-aggregates mediated by break the hydrosaline bridges between Asp 23 and Lys 28, was are key element for amyloid dimerization. The amyloid pore/ channel hypothesis has been explored only in neuronal models, however recently experiments suggested the frog oocytes such an excellent model to explore the mechanism of the amyloid pore/channel hypothesis. So, the used of frog oocytes to explored the mechanism of amyloid aggregates is new, mainly for amyloid/pore hypothesis. Therefore, this experimental model is a powerful tool to explore the mechanism implicates in the Alzheimer's disease pathology and also suggests a model to prevent the Alzheimer's disease pathology.

• Molecules and Cells
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• 제46권11호
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• pp.675-687
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• 2023

Accumulation of pathogenic amyloid-β disrupts the tight junction of retinal pigment epithelium (RPE), one of its senescence-like structural alterations. In the clearance of amyloid-β, the autophagy-lysosome pathway plays the crucial role. In this context, mammalian target of rapamycin (mTOR) inhibits the process of autophagy and lysosomal degradation, acting as a potential therapeutic target for age-associated disorders. However, efficacy of targeting mTOR to treat age-related macular degeneration remains largely elusive. Here, we validated the therapeutic efficacy of the mTOR inhibitors, Torin and PP242, in clearing amyloid-β by inducing the autophagy-lysosome pathway in a mouse model with pathogenic amyloid-β with tight junction disruption of RPE, which is evident in dry age-related macular degeneration. High concentration of amyloid-β oligomers induced autophagy-lysosome pathway impairment accompanied by the accumulation of p62 and decreased lysosomal activity in RPE cells. However, Torin and PP242 treatment restored the lysosomal activity via activation of LAMP2 and facilitated the clearance of amyloid-β in vitro and in vivo. Furthermore, clearance of amyloid-β by Torin and PP242 ameliorated the tight junction disruption of RPE in vivo. Overall, our findings suggest mTOR inhibition as a new therapeutic strategy for the restoration of tight junctions in age-related macular degeneration.

• 생명과학회지
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• 제15권2호
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• pp.169-175
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• 2005

Resveratrol (3,4',5-trihydroxy-trans-stilbene)은 포도와 같은 식물에서 각종 감염균으로부터 자신의 몸을 보호하기 위하여 생성되는 물질인 phytoalexin의 일종으로 강력한 항산화작용, 암예방 효과 및 항암 작용을 포함한 각종 약리작용을 가진 것으로 보고 되어져 오고 있다. Alzheimer 환자의 뇌에 축적되어 뇌 신경세포를 죽이는 amyloid plaque의 주 성분은 $amyloid-\beta$의 축적에 의한 것인데, $amyloid-\beta$는 정상적인 단백질 신진대사 과정의 결과로 체내 모든 세포들로부터 생성되는 물질이다. 본 연구에서는 resveratrol의 세포독성 보호효과에 관한 효능을 검증하기 위하여 C6 신경교세포에서 $amyloid-\beta-peptide$ (fragment 31-35)에 의한 세포독성 및 세포성장 조절관련 주요 유전자들의 발현에 미치는 resveratrol의 영향을 조사하였다. $Amyloid-\beta$가 처리된 C6세포는 처리 농도의존적으로 증식이 억제되었으며, 형태적 변형도 유발 되었으나 resveratrol의 전처리에 의하여 효과적으로 차단되었다. RT-PCR 및 Western blot analysis에 의한 결과에서 $amyloid-\beta$ 처리에 의한 세포증식 억제는 종양억제유전자 p53 및 Cdk 억제제인 p21 (WAF1/CIP1) 발현이 증가되었다. 또한 apoptosis 유발에 매우 중요한 역할을 수행하는 Bax의 발현도 $amyloid-\beta$가 처리된 C6 세포에서 발현이 증가되었으나 apoptosis 유발억제에 관여하는 Bcl-2및 $Bcl-X_{L}$ 발현에는 큰 영향을 미치지 못하였다. 그러나 resveratrol이 전처리된 세포에서는 처리 농도 의존적으로 $amyloid-\beta$에 의해 유도되는 p53, p21 및 Bax의 발현이 정상수준으로 회복되었다.