• 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.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.290-294
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• 2021

Extracellular beta amyloid (Aβ) plaques are the neuropathological hallmarks of Alzheimer's disease (AD). Accordingly, reducing Aβ levels is considered a promising strategy for AD prevention. 3'-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside significantly decreased the Aβ production and this effect was accompanied with reduced sAPPβ production known as a soluble ectodomain APP fragment through β-secretases in HeLa cells overexpressing amyloid precursor proteins (APPs). This compound also increased the level of sAPPα, which is a proteolytic fragment of APP by α-secretases. In addition, 3'-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside decreased the protein level of β-secretases, but the protein levels of A disintegrin and metalloproteinase (ADAM) family, especially ADAM10 and ADAM17, are increased. Thus, 3'-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside could be useful in the development of AD treatment in the aspect of amyloid pathology.

• 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.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제24권1호
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• pp.39-46
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• 2020

Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia worldwide, and is mainly characterized by aggregated β-amyloid (Aβ). Increasing evidence has shown that plant extracts have the potential to delay AD development. The plant sterol β-Sitosterol has a potential role in inhibiting the production of platelet Aβ, suggesting that it may be useful for AD prevention. In the present study, we aimed to investigate the effect and mechanism of β-Sitosterol on deficits in learning and memory in amyloid protein precursor/presenilin 1 (APP/PS1) double transgenic mice. APP/PS1 mice were treated with β-Sitosterol for four weeks, from the age of seven months. Brain Aβ metabolism was evaluated using ELISA and Western blotting. We found that β-Sitosterol treatment can improve spatial learning and recognition memory ability, and reduce plaque load in APP/PS1 mice. β-Sitosterol treatment helped reverse dendritic spine loss in APP/PS1 mice and reversed the decreased hippocampal neuron miniature excitatory postsynaptic current frequency. Our research helps to explain and support the neuroprotective effect of β-Sitosterol, which may offer a novel pharmaceutical agent for the treatment of AD. Taken together, these findings suggest that β-Sitosterol ameliorates memory and learning impairment in APP/PS1 mice and possibly decreases Aβ deposition.

• 동의생리병리학회지
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• 제18권1호
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• pp.53-57
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• 2004

In order to evaluate the neuroprotective effects of Kamisinsunbulo-dan(KSM), the cytotoxicity of amyloid β and the recovering effect of KSM were checked at first. Then the viability of C6 cells was tested in comparison with each concentration of KSM. The cytotoxicity of amyloid β(31-35) showed from 5 μM higher to 100 μM. And the recovering effect by KSM showed significantly at 100㎍/㎖. concentration. And the cell viability was shown significantly over 200 ㎍/㎖ of KSM. This is thought that the viability has some relation to length of culturing duration, 6 to 12 hrs. Lastly in the western blotting of APP, the amount of low molecule's APP was decreased. So the APP form ratio(APPr) changed to increase, and it meant that KSM can be used to lower the toxic APP, and can be a candidate for Alzheimer's disease.

• The Journal of Korean Physical Therapy
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• 제33권3호
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• pp.136-141
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• 2021

Purpose: Dementia is a disease in which cognitive function declines, leading to deterioration of body functions and activities of daily living. The purpose of this study is to explore the effects of dual-task training, including cognitive tasks, on cognitive and body function and β-amyloid levels in Alzheimer's dementia patients. Methods: 34 inpatients diagnosed with Alzheimer's dementia at a nursing hospital located in South Korea. The patients were randomly divided into a dual-task group (n=16) and a single-task group (n=18). Each group was trained for 30 minutes three times a week for eight weeks. The MMSE-K was used to measure the patients' cognitive function. To assess the patients' static balance ability, their LOS was measured using BioRescue. while dynamic balance was measured using the BBS. The 10MWT were conducted to evaluate the patients' walking ability. Blood analysis was performed to measure levels of β-amyloid. Results: Both groups exhibited statistically significant improvements in gait function after the training (p<0.05). The dual-task group exhibited statistically significant differences in cognitive function, static and dynamic balance function, and β-amyloid levels after training (p<0.05). A significant difference was observed between the two groups (p<0.05). Conclusion: Dual-task training were found to be effective in improving cognitive and bodily functioning and reducing β-amyloid levels in Alzheimer's dementia patients. Thus, this may be suggested as an effective exercise method for the treatment and early prevention of Alzheimer's dementia.

• Bulletin of the Korean Chemical Society
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• 제29권12호
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• pp.2331-2336
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• 2008

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

• Bulletin of the Korean Chemical Society
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• 제22권10호
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• pp.1065-1066
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• 2001