• 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.

• 대한치매학회지
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• 제21권4호
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• pp.126-137
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• 2022

Background and Purpose: Early detection of subjective cognitive decline (SCD) due to Alzheimer's disease (AD) is important for clinical research and effective prevention and management. This study examined if quantitative electroencephalography (qEEG) could be used for early detection of AD in SCD. Methods: Participants with SCD from 6 dementia clinics in Korea were enrolled. ¹⁸F-florbetaben brain amyloid positron emission tomography (PET) was conducted for all the participants. qEEG was performed to measure power spectrum and source cortical activity. Results: The present study included 95 participants aged over 65 years, including 26 amyloid PET (+) and 69 amyloid PET (-). In participants with amyloid PET (+), relative power at delta band was higher in frontal (p=0.025), parietal (p=0.005), and occipital (p=0.022) areas even after adjusting for age, sex, and education. Source activities of alpha 1 band were significantly decreased in the bilateral fusiform and inferior temporal areas, whereas those of delta band were increased in the bilateral cuneus, pericalcarine, lingual, lateral occipital, precuneus, posterior cingulate, and isthmus areas. There were increased connections between bilateral precuneus areas but decreased connections between left rostral middle frontal area and bilateral frontal poles at delta band in participants with amyloid PET (+) showed. At alpha 1 band, there were decreased connections between bilateral entorhinal areas after adjusting for covariates. Conclusions: SCD participants with amyloid PET (+) showed increased delta and decreased alpha 1 activity. qEEG is a potential means for predicting amyloid pathology in SCD. Further longitudinal studies are needed to confirm these findings.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2003년도 추계학술대회
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• pp.139-140
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• 2003

• BMB Reports
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• 제43권10호
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• pp.656-663
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• 2010

Amyloid precursor protein (APP), which is critically involved in the pathogenesis of Alzheimer's disease (AD), is cleaved by gamma/epsilon-secretase activity and results in the generation of different lengths of the APP Intracellular C-terminal Domain (AICD). In spite of its small size and short half-life, AICD has become the focus of studies on AD pathogenesis. Recently, it was demonstrated that AICD binds to different intracellular binding partners ('adaptor protein'), which regulate its stability and cellular localization. In terms of choice of adaptor protein, phosphorylation seems to play an important role. AICD and its various adaptor proteins are thought to take part in various cellular events, including regulation of gene transcription, apoptosis, calcium signaling, growth factor, and $NF-{\kappa}B$ pathway activation, as well as the production, trafficking, and processing of APP, and the modulation of cytoskeletal dynamics. This review discusses the possible roles of AICD in the pathogenesis of neurodegenerative diseases including AD.

• 생약학회지
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• 제38권4호
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• pp.308-311
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• 2007

Inhibition of acetylcholinesterase and amyloid beta(1-42) peptide is good drug targets for Alzheimer's disease therapeutics. Among the twenty enthusiasm reducing herbals, the 70% methanol extracts (1 mg/ml) of Moutan Radicis Cortex and Forsythiae Fructus showed 91.5% and 85.3% about acethylcholinesterase inhibition, respectively. The extracts (1 mg/ml) of Coptidis Rhizoma and Paeoniae Radix Rubra showed more than 85% inhibition rate against amyloid beta (1-42) peptide aggregation. The neuroprotective effect of the extracts (1 mg/ml) of Moutan Radicis Cortex, Forsythiae Fructus and Paeoniae Radix Rubra showed 90.0%, 87.4% and 85.1% to compare with amyloid beta (1-42) peptide treated cells (IMR-32), respectively. Three herbs, Moutan Radicis Cortex, Forsythiae Fructus and Paeoniae Radix Rubra are promising candidates from natural products for development of Alzheimer's disease therapeutics.

• 대한한방내과학회지
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• 제27권1호
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• pp.253-264
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• 2006

Object: This research investigated effects of Jujadokseo-hwan on mice with Alzheimer's Disease induced by $amyloid-{\beta}$. According to Dongyibogam, Jujadokseo-hwan can cure amnesia. Amyloid-B is believed to induce oxidative stress and inflammation in the brain, postulated to play important roles in the pathogenesis of Alzheimer's disease. In this way $Amyloid-{\beta}$ induces Alzheimer's Disease. Methods : In order to make an efficient prescription and cope with dementia, learning and memory functions of mice were tested on passive avoidance test and V-maze task. $NF-{\kappa}B$ were measured from protein derived from the brain. RT-PCR was done for !gene analysis. Primers were protein kinase Band $NGF-{\alpha}$. Results : 1. Jujadokseo-hwan was effective for memory capacity on passive avoidance test. but noneffective for spatial memory capacity and locomotor activity on Y -maze task. 2. The measurement of $NF-{\kappa}B$ showed upward tendancies and the result of RT-PCR showed up-regulation when given Jujadokseo-hwan by mouth. Conclusion: Results suggest that Jujadokseo-hwan is effective on mice with Alzheimer's Disease induced by $amyloid-{\beta}$.

• Bulletin of the Korean Chemical Society
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• 제35권2호
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• pp.425-430
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• 2014

Amyloidogenic proteins often exhibit fibrillar polymorphism through alternative assembly processes, which has been considered to have possible pathological implications. Here, firefly luciferase (LUC) is shown to induce amyloid polymorphism of ${\alpha}$-synuclein, the major constituent of Lewy bodies found in Parkinson's disease, by acting as a novel template. The drastically accelerated fibrillation kinetics of ${\alpha}$-synuclein with LUC required the nucleation center produced by the active enzyme of LUC. Fluorescent dye binding, transmission electron microscopy, and Fourier transformed infrared spectroscopy revealed the morphologically distinctive amyloid fibrils of ${\alpha}$-synuclein prepared in the absence or presence of LUC. As the altered morphological characteristics became inherent to the mature fibrils, those properties were inherited to next-generations via nucleation-dependent fibrillation process. The seed control, therefore, would be an effective means to modify amyloid fibrils with different biochemical characteristics. In addition, the LUC-directed amyloid fibrillar polymorphism also suggests that other cellular biomolecules including enzymes in general are able to diversify amyloid fibrils, which could be self-propagated with diversified biological activities, if any, inside cells.

• Biomolecules & Therapeutics
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• 제27권3호
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• pp.276-282
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• 2019

${\beta}$-amyloid precursor protein (APP) can be cleaved by ${\alpha}$-, and ${\gamma}$-secretase at plasma membrane producing soluble ectodomain fragment ($sAPP{\alpha}$). Alternatively, following endocytosis, APP is cleaved by ${\beta}$-, and ${\gamma}$-secretase at early endosomes generating ${\beta}$-amyloid ($A{\beta}$), the main culprit in Alzheimer's disease (AD). Thus, APP endocytosis is critical for $A{\beta}$ production. Recently, we reported that Monsonia angustifolia, the indigenous vegetables consumed in Tanzania, improved cognitive function and decreased $A{\beta}$ production. In this study, we examined the underlying mechanism of justicidin A, the active compound of M. angustifolia, on $A{\beta}$ production. We found that justicidin A reduced endocytosis of APP, increasing $sAPP{\alpha}$ level, while decreasing $A{\beta}$ level in HeLa cells overexpressing human APP with the Swedish mutation. The effect of justicidin A on $A{\beta}$ production was blocked by endocytosis inhibitors, indicating that the decreased APP endocytosis by justicidin A is the underlying mechanism. Thus, justicidin A, the active compound of M. angustifolia, may be a novel agent for AD treatment.

• 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.

• BMB Reports
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• 제57권6호
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• pp.263-272
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• 2024

Amyloid-β (Aβ) is one of the amyloidogenic intrinsically disordered proteins (IDPs) that self-assemble to protein aggregates, incurring cell malfunction and cytotoxicity. While Aβ has been known to regulate multiple physiological functions, such as enhancing synaptic functions, aiding in the recovery of the blood-brain barrier/brain injury, and exhibiting tumor suppression/antimicrobial activities, the hydrophobicity of the primary structure promotes pathological aggregations that are closely associated with the onset of Alzheimer's disease (AD). Aβ proteins consist of multiple isoforms with 37-43 amino acid residues that are produced by the cleavage of amyloid-β precursor protein (APP). The hydrolytic products of APP are secreted to the extracellular regions of neuronal cells. Aβ 1-42 (Aβ42) and Aβ 1-40 (Aβ40) are dominant isoforms whose significance in AD pathogenesis has been highlighted in numerous studies to understand the molecular mechanism and develop AD diagnosis and therapeutic strategies. In this review, we focus on the differences between Aβ42 and Aβ40 in the molecular mechanism of amyloid aggregations mediated by the two additional residues (Ile41 and Ala42) of Aβ42. The current comprehension of Aβ42 and Aβ40 in AD progression is outlined, together with the structural features of Aβ42/Aβ40 amyloid fibrils, and the aggregation mechanisms of Aβ42/Aβ40. Furthermore, the impact of the heterogeneous distribution of Aβ isoforms during amyloid aggregations is discussed in the system mimicking the coexistence of Aβ42 and Aβ40 in human cerebrospinal fluid (CSF) and plasma.