• 한국방사선학회논문지
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• 제10권5호
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• pp.307-312
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• 2016

알츠하이머병은 치매를 일으키는 가장 흔한 퇴행성 뇌 질환이다. 뇌에 축적되는 베타 아밀로이드 단백질은 기억력감퇴, 언어능력 저하등 일상생활 수행 능력이 어렵게 된다. 베타 아밀로이드 플라그 농도는 인지장애를 가진 성인환자에서 알츠하이머 질환과 인지장애의 다른 원인인지를 평가하는 데 사용된다. 베타아밀로이드 단백질에 대한 높은 민감성과 특이성을 가진 $^{18}F$-Florbetaben을 이용하여 알츠하이머병을 조기진단에 유용성을 알아보고자 한다. $^{18}F$-FDG Brain 영상에서 특이소견 없음을 보인다. 그리고 MR-Brain 영상에서 해마의 위축이 없는 것으로 보였다. 하지만 $^{18}F$-Florobetaben에서 베타 아밀로이드의 섭취는 알츠하이머병의 진전이 되고 있음을 알려준다. 따라서, $^{18}F$-Florobetaben은 알츠하이머병을 조기 진단하는 데 매우 유용하다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.204.1-204.1
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• 2003

Azheimer's Disease (AD) known as senile dementia accounts for 50％ of all dementia cases and is in growing status as population goes up. Generally. AD is a progressive neurodegenerative disease and includes much of senile plaque in cerebral hippocampus and cortex in patient's brain. For decades. AD theory is explained by amyloid cascade hypothesis. In process of the hypothesis, amyloid hypothesis forms fibrillar form beta-amyloid peptide (A${\beta}$ peptide) and extraordinarily accumulates in brain tissue, and lastly senile plaque is formed, which pathologically affect the brain. (omitted)

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2006년도 Spring Conference
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• pp.121-135
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• 2006

• Fisheries and Aquatic Sciences
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• 제21권5호
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• pp.13.1-13.8
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• 2018

Amyloid plaque, also called senile plaque, the product of aggregation of ${\beta}$-amyloid peptides ($A{\beta}$), is observed in brains of the patients with Alzheimer's disease (AD) and is one of the key factors in etiology of the disease. In this study, hydrolysates obtained from the sea hare (Aplysia kurodai) were investigated for ${\beta}$-secretase inhibitory peptide. The sea hare's muscle protein was hydrolyzed using six enzymes in a batch reactor. Trypsin hydrolysate had highest ${\beta}$-secretase inhibitory activity compared to the other hydrolysates. ${\beta}$-secretase inhibitory peptide was separated using Sephadex G-25 column chromatography and high-performance liquid chromatography on a C18 column. ${\beta}$-secretase inhibitory peptide was identified as eight amino acid residues of Val-Ala-Ala-Leu-Met-Leu-Phe-Asn by N-terminal amino acid sequence analysis. $IC_{50}$ value of purified ${\beta}$-secretase inhibitory peptide was $74.25{\mu}M$, and Lineweaver-Burk plots suggested that the peptide purified from sea hare muscle protein acts as a competitive inhibitor against ${\beta}$-secretase. Results of this study suggest that peptides derived from sea hare muscle may be beneficial as anti-dementia compounds in functional foods or as pharmaceuticals.

• 대한의생명과학회지
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• 제25권1호
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• pp.7-14
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• 2019

Alzheimer's disease (AD) is highly prevalent in dementia, with no specifically effective treatment having yet been discovered. Amyloid plaques are one of the key hallmarks of AD. Transgenic mouse models exhibiting Alzheimer's disease-like pathology have been widely used to study the pathophysiology of Alzheimer's disease. In this study, we showed an age-dependent correlation between cognitive function, pathological findings, and [F-18] Florbetaben (FBB) PET images. Nineteen transgenic mice (12 with AD, 7 with controls) were used for this study. We observed an increase in ${\beta}$-Amyloid deposition ($A{\beta}$) in brain tissue and [F-18] FBB amyloid PET imaging in the AD group. The [F-18] FBB data showed a mildly negative trend with cognitive function. Pathological findings were negatively correlated with cognitive functions. These finding suggests that amyloid beta deposition can be well-monitored with [F-18] FBB PET and a decline in cognitive function is related to the increase in amyloid plaque burden.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.136.1-136.1
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• 2003

$\beta$-amyloid (A$\beta$) peptide produced from amyloid precursor protein (APP) is a major cause of Alzheimer's disease (AD). Therefore, in early phase of AD, imbalance of the production and the clearance of $A\beta$ is regarded as an important factor to progressive AD presenting senile plaque, a hallmark of AD. In the present study, we wanted to verify whether Rg3 can playa role in helping microglia engulfing $A\beta$ peptides. Validations for the study was conducted by using DiI-Ac-LDL, which attached only on type A macrophage scavenger receptor (MSR-A) and ligands for he receptor, fucoidan. (omitted)

• 한국키틴키토산학회지
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• 제23권4호
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• pp.220-227
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• 2018

Amyloid plaque is a product of aggregation of ${\beta}$-amyloid peptide ($A{\beta}$) and is an important factor in the pathogenesis of Alzheimer's Disease (AD). $A{\beta}$ is a major component of amyloid plaque and vascular deposits in the AD brain. The enzyme ${\beta}$-secretase is required for the production of $A{\beta}$; thus, prevention of the formation of $A{\beta}$ through the inhibition of ${\beta}$-secretase is a major focus in the study of the treatment of AD. In this study, we investigated ${\beta}$-secretase inhibitory activity of an Arctoscopus japonicus peptide. An Alcalase hydrolysate had the highest ${\beta}$-secretase inhibitory activity. A ${\beta}$-secretase inhibitory activity peptide was separated using ion exchange column chromatography (carboxy-methyl: CM, quaternary methyl ammonium: QMA) and reverse phase high performance liquid chromatography (RP-HPLC) on a C18 column. The $IC_{50}$ value of the purified peptide was $248.2{\pm}1.73{\mu}g/mL$. The ${\beta}$-secretase inhibitory peptide was identified as a six amino acid residue of Gly-Pro-Val-Gly-Ala-Pro (MW: 497.27 Da). In cell viability experiments, the final purified fraction, the carboxy-methyl ion exchange column fraction (CM-F1) showed no significant cytotoxic effect in SH-SY5Y cells at concentrations below $100{\mu}g/mL$ in 24 h. The results of this study suggest that peptides separated from Arctoscopus japonicus may be beneficial as ${\beta}$-secretase inhibitor compounds in functional foods.

• 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.

• 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.

• 동의생리병리학회지
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• 제19권1호
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• pp.242-245
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• 2005

The most common feature of neurodegenerative disease (i.e. Alzheimer's disease, AD) is the increased number of activated microglial cells nearby the pathogenic area of the brain, such as amyloid plaque in AD. An abnormality of protein regulation and an imbalance of clearance against ${\beta}-amyloid\;(A{\beta})$ produced amyloid precursor protein (APP) can turn microglia into the activated feature out of the ramified resting phase. We examined the possibility that ginsenoside Rb1 could attenuate the microglial activation induced by massive $A{\beta}$ that has known to induce a chronic inflammation, which is a major cause of AD by damaging neuronal cells (i.e. apoptosis or necrosis). Aggregated $A{\beta}42\;(5\;{\mu}M)$ peptide was used with lipopolysaccharide (LPS) ($10\;{\mu}g$) for a comparative control up to 48hours. We found that Rb1 reduced the production of nitric oxide as well as proinflammatory cytokines, such as $IL-1{\beta}$ and $TNF-{\alpha}$.