• Journal of Acupuncture Research
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• 제23권2호
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• pp.33-46
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• 2006

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disease associated with aging in the human population. This disease is characterized by the extracellular deposition of beta-amyloid peptide $(A{\beta})$ in cerebral plaques. $A{\beta}$ is derived from the ${\beta}-amyloid$ precursor protein (APP) by the enzymes, ${\beta}-$ and ${\eta}o-secretase$. Compounds that ${\beta}-$ or ${\eta}o-secretase$ inhibit activity, can reduce the production of $A{\beta}$ peptides, and thus have therapeutic potential in the treatment of AD. Increasing body of evidence has been demonstrated that Bee Venom(BV) Acupuncture could compete with complex protein involving in multiple step of $NF-{\kappa}B$ activation and exert the anti-inflammatory potential of combined inhibition of the prostanoid and nitric oxide synthesis systems by inhibition of IKK and $NF-{\kappa}B$. In this study, I investigated possible effects of BV on memory dysfunction caused by lipopolysaccharide (LPS) and $A{\beta}$ through inhibition of secretases activities and $A{\beta}$ aggregation. I examined the improving effect of BV on the LPS (2.5 mg/Kg, i.p.)-induced memory dysfunction using passive avoidance response and water maze tests in the mice. BV (0.84, $1.67\;{\mu}g/ml$) reversed the LPS-induced memorial dysfunction in dose dependent manner. BV also dose-dependently attenuated LPS-induced ${\beta}$ and ${\eta}o-secretase$ activities in cerebral cortex and hippocampus of the mice brain. This study therefore suggests that BV acupuncture method may be useful for prevention of development or progression of AD.

• Bulletin of the Korean Chemical Society
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• 제35권7호
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• pp.2065-2071
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• 2014

${\beta}$-Secretase (beta-amyloid converting enzyme 1 [BACE1]) is involved in the first and rate-limiting step of ${\beta}$-amyloid ($A{\beta}$) peptides production, which leads to the pathogenesis of Alzheimer's disease(AD). Therefore, inhibition of BACE1 activity has become an efficient approach for the treatment of AD. Ligand-based and docking-based 3D-quantitative structure-activity relationship (3D-QSAR) studies of acyl guanidine analogues were performed with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) to obtain insights for designing novel potent BACE1 inhibitors. We obtained highly reliable and predictive CoMSIA models with a cross-validated $q^2$ value of 0.725 and a predictive coefficient $r{^2}_{pred}$ value of 0.956. CoMSIA contour maps showed the structural requirements for potent activity. 3D-QSAR analysis suggested that an acyl guanidine and an amide group in the $R_6$ substituent would be important moieties for potent activity. Moreover, the introduction of small hydrophobic groups in the phenyl ring and hydrogen bond donor groups in 3,5-dichlorophenyl ring could increase biological activity.

• 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.82.2-83
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• 2003

Beta-amyloid peptide (A${\beta}$) is considered to be responsible for the pathogenesis of the Alzheimer's disease. Several lines of evidence support that A${\beta}$-amyloid-induced cytotoxicity is mediated through the generation of reactive oxygen species (ROS). Agents that are able to scavenge excess ROS may be useful as protecting or reducing agents for development or progress of AD. Green tea extract has been known to have antioxidant property. Our previous studies also demonstrate that green tea extract protected ischemia/reperfusion-induced brain injury by reduction of cell death through scavenging of oxidative damages of macromolecules. (omitted)

• 대한한의학회지
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• 제35권4호
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• pp.10-23
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• 2014

Objectives: This study evaluated the effects of Guibi-tang (GBT) on neuronal apoptosis and cognitive impairment induced by beta amyloid ($A{\beta}$), (1-42) injection in the hippocampus of ICR mice. Methods: $A{\beta}$ (1-42) was injected unilaterally into the lateral ventricle using a Hamilton syringe and micropump ($2{\mu}g/3{\mu}{\ell}$, $0.6{\mu}{\ell}/min$). Water extract of GBT was administered orally once a day (500 mg/kg) for 3 weeks after the $A{\beta}$ (1-42) injection. Acquisition of learning and retention of memory were tested using the Morris water maze. Neuronal damage and $A{\beta}$ accumulation in the hippocampus was observed using cresyl violet and Congo red staining. The anti-apoptotic effect of GBT was evaluated using TUNEL labeling in the hippocampus. Results: GBT significantly shortened the escape latencies during acquisition training trials. GBT significantly increased the number of target headings to the platform site, the swimming time spent in the target quadrant, and significantly shortened the time for the 1st target heading during the retention test trial. GBT significantly attenuated the reduction in thickness and number of CA1 neurons, and $A{\beta}$ accumulation in the hippocampus produced by $A{\beta}$ (1-42) injection. GBT significantly reduced the number of TUNEL-labeled neurons in the hippocampus. Conclusion: These results suggest that GBT improved cognitive impairment by reducing neuronal apoptosis and $A{\beta}$ accumulation in the hippocampus. GBT may be a beneficial herbal formulation in treating cognitive impairment including Alzheimer's disease.

• Biomolecules & Therapeutics
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• 제23권2호
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• pp.156-164
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• 2015

Alzheimer's disease (AD) is a neurodegenerative disorder associated with progressive memory loss and neuronal cell death. Although numerous previous studies have been focused on disease progression or reverse pathological symptoms, therapeutic strategies for AD are limited. Alternatively, the identification of traditional herbal medicines or their active compounds has received much attention. The aims of the present study were to characterize the ameliorating effects of spinosin, a C-glucosylflavone isolated from Zizyphus jujuba var. spinosa, on memory impairment or the pathological changes induced through amyloid-${\beta}_{1-42}$ oligomer ($A{\beta}O$) in mice. Memory impairment was induced by intracerebroventricular injection of $A{\beta}O$ ($50{\mu}M$) and spinosin (5, 10, and 20 mg/kg) was administered for 7 days. In the behavioral tasks, the subchronic administration of spinosin (20 mg/kg, p.o.) significantly ameliorated $A{\beta}O$-induced cognitive impairment in the passive avoidance task or the Y-maze task. To identify the effects of spinosin on the pathological changes induced through $A{\beta}O$, immunohistochemistry and Western blot analyses were performed. Spinosin treatment also reduced the number of activated microglia and astrocytes observed after $A{\beta}O$ injection. In addition, spinosin rescued the $A{\beta}O$-induced decrease in choline acetyltransferase expression levels. These results suggest that spinosin ameliorated memory impairment induced through $A{\beta}O$, and these effects were regulated, in part, through neuroprotective activity via the anti-inflammatory effects of spinosin. Therefore, spinosin might be a useful agent against the amyloid ${\beta}$ protein-induced cognitive dysfunction observed in AD patients.

• 한국자원식물학회지
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• 제26권4호
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• pp.417-425
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• 2013

본 연구에서는 도라지 추출물에 대한 세포 독성을 확인하였으며, $A{\beta}$에 의한 PC12 세포 독성에 대한 보호효과를 관찰하였다. 또한 도라지 추출물과 도라지 추출물 연양갱을 4주간 강제 경구 투여하여 Morris 수중미로시험에서 도달지점까지의 도달시간이 도라지 추출물 및 도라지 추출물 연양갱 투여에 의해서 모두에서 유의하게 감소하였다. 이와 유사하게 수동회피시험에서도 자극이 있는 어두운 방을 나오는 시간이 도라지 추출물 및 도라지 추출물 연양갱 투여에 의해서 현저하게 감소하였다. 따라서 도라지 추출물 및 도라지 추출물 연양갱은 인지능 개선에 도움을 줄 것으로 생각된다.

• 한국산학기술학회논문지
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• 제20권11호
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• pp.115-120
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• 2019

본 연구는 경증 알츠하이머 치매 노인의 베타 아밀로이드 및 혈중 지질 수준과 인지기능 간의 상관관계를 알아보고자 실시하였다. 연구의 대상자는 경증 알츠하이머 치매 노인 45명을 대상으로 실시하였다. 2018년 12월 베타 아밀로이드 및 혈중 지질 수준을 측정하기 위해 혈액 분석을 실시하였으며, 인지기능의 측정을 위해 MMSE-K 검사를 이용하여 측정하였다. 베타 아밀로이드 및 혈중 지질 수준과 인지기능 간의 상관관계를 알아보기 위해 Pearson's correlation analysis를 사용하여 분석하였다. 연구 결과 베타 아밀로이드 수준과 인지기능 간의 상관관계에서는 -.604로 유의한 음의 상관관계를 보였으며(p<.05), 혈중 지질 수준과 인지기능 간의 상관관계에서는 TC(total cholesterol)와 LDL(low density lipoprotein) 수준에서 각각 -.601, -.403로 유의한 음의 상관관계를 보였다(p<.05). 이와 같은 결과는 베타아밀로이드 및 TC, LDL 수준이 증가할수록 인지기능이 감소하는 음의 상관관계가 나타나는 것을 알 수 있었다. 이처럼 치매 환자의 예방 및 인지기능의 증진을 위해서 치매 관련 병리학적 인자의 관리가 중요하다고 사료된다.

• Bulletin of the Korean Chemical Society
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• 제28권12호
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• pp.2283-2287
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• 2007

Amyloid fibril formation of amyloid β/A4 protein (Aβ) is critical to understand the pathological mechanism of Alzheimer's disease and develop controlling strategy toward the neurodegenerative disease. For this purpose, dequalinium (DQ) has been employed as a specific modifier for Aβ aggregation and its subsequent cytotoxicity. In the presence of DQ, the final thioflavin-T binding fluorescence of Aβ aggregates decreased significantly. It was the altered morphology of Aβ aggregates in a form of the bundles of the fibrils, distinctive from normal single-stranded amyloid fibrils, and the resulting reduced β-sheet content that were responsible for the decreased fluorescence. The morphological transition of Aβ aggregates assessed with atomic force microscope indicated that the bundle structure observed with DQ appeared to be resulted from the initial multimeric seed structure rather than lateral association of preformed single-stranded fibrils. Investigation of the seeding effect of the DQ-induced Aβ aggregates clearly demonstrated that the seed structure has determined the final morphology of Aβ aggregates as well as the aggregative kinetics by shortening the lag phase. In addition, the cytotoxicity was also varied depending on the final morphology of the aggregates. Taken together, DQ has been considered to be a useful chemical probe to control the cytotoxicity of the amyloid fibrils by influencing the seed structures which turned out to be central to develop therapeutic strategy by inducing the amyloid fibrils in different shapes with varied toxicities.

• 대한물리의학회지
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• 제15권2호
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• pp.23-30
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• 2020

PURPOSE: The purpose of this study was to examine the effects of dual-task training with cognitive tasks on cognitive functions and β-amyloid levels in the elderly with mild dementia. METHODS: The subjects were 36 elderly inpatients diagnosed with mild dementia at S Hospital located in Gyeongsangbuk-do, South Korea. The patients were randomly divided into a dual-task training group (DTG; n = 18) or a single-task training group (STG; n = 18). DTG performed dual-task training with cognitive tasks while STG performed only exercise tasks. These groups performed their respective exercises during a 30-minute session occurring three times a week over an 8-week period. MMSE-K and GDS were used to measure the subjects' cognitive function. To assess the subjects' dementia-related factors, their β-amyloid levels were measured by blood analysis. RESULTS: The results of the experiment were as follows: DTG showed statistically significant differences between their MMSE-K scores and β-amyloid levels before and after training (p < .05), whereas they exhibited no statistically significant differences in their GDS scores. MMSE-K scores and β-amyloid levels were significantly different between DTG and STG after training. CONCLUSION: The present study's overall results indicate that dual-task training with cognitive tasks is more effective than single-task training in improving cognitive functions and β-amyloid levels in the elderly with mild dementia. In other words, regular dual-task training can be considered as effective in improving cognitive function and dementia-related factors in the elderly with mild dementia and thus may be suggested as an effective exercise method for the treatment and early prevention of dementia.

• BMB Reports
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• 제43권10호
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• pp.649-655
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• 2010

Alzheimer's disease (AD) is the most common age-dependent neurodegenerative disorder and shows progressive memory loss and cognitive decline. Intraneuronal filaments composed of aggregated hyperphosphorylated tau protein, called neurofibrillary tangles, along with extracellular accumulations of amyloid $\beta$ protein (A$\beta$), called senile plaques, are known to be the neuropathological hallmarks of AD. In light of recent studies, epigenetic modification has emerged as one of the pathogenic mechanisms of AD. Epigenetic changes encompass an array of molecular modifications to both DNA and chromatin, including transcription factors and cofactors. In this review, we summarize how DNA methylation and changes to DNA chromatin packaging by post-translational histone modification are involved in AD. In addition, we describe the role of SIRTs, histone deacetylases, and the effect of SIRT-modulating drugs on AD. Lastly, we discuss how amyloid precursor protein (APP) intracellular domain (AICD) regulates neuronal transcription. Our understanding of the epigenomes and transcriptomes of AD may warrant future identification of novel biological markers and beneficial therapeutic targets for AD.