• Biomolecules & Therapeutics
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• v.29 no.3
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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.

• Journal of Oriental Neuropsychiatry
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• v.21 no.2
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• pp.191-200
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• 2010

Objectives : This experiment was designed to investigate the effect of Chongmyung-Tang Prescription Combination(CmTP-$C_{1-10}$) extract on the production of amyloid $\beta$ protein and $\beta$-site amyloid precursor protein-cleaving enzyme(BACE) activity. Methods : The effect of CmTP-$C_{1-10}$ extract on expression of APP mRNA, BACE2 mRNA in BV2 microglia cell line treated by lipopolysacchride(LPS) and amyloid $\beta$ protein fragment(A$\beta$ fragment) were investigated. The effect of CmTP-$C_{1-10}$ extract on production of amyloid $\beta$ protein(A$\beta$) in BV2 microglia cell line treated by LPS and A$\beta$ fragment were investigated. The effect of CmTP-$C_{1-10}$ extract on BACE activity were investigated. Results : 1. CmTP-$C_9$ extract the most significantly suppressed the expression of APP mRNA, BACE2 mRNA in BV2 microglia cell line treated by LPS and A$\beta$ fragment. 2. CmTP-$C_9$ extract significantly suppressed the production of A$\beta$ in BV2 microglia cell line treated by LPS and A$\beta$ fragment. 3. CmTP-$C_9$ extract the most significantly inhibited BACE activity. Conclusions : These results suggest that CmTP-$C_9$ may be effective for the prevention and treatment of Alzheimer's Disease. Investigation into clinical use of CmTP-$C_9$ for Alzheimer's Disease is suggested for future research.

• BMB Reports
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• v.49 no.6
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• pp.337-343
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• 2016

Understanding of trafficking, processing, and degradation mechanisms of amyloid precursor protein (APP) is important because APP can be processed to produce β-amyloid (Aβ), a key pathogenic molecule in Alzheimer's disease (AD). Here, we found that APP contains KFERQ motif at its C-terminus, a consensus sequence for chaperone-mediated autophagy (CMA) or microautophagy which are another types of autophagy for degradation of pathogenic molecules in neurodegenerative diseases. Deletion of KFERQ in APP increased C-terminal fragments (CTFs) and secreted N-terminal fragments of APP and kept it away from lysosomes. KFERQ deletion did not abolish the interaction of APP or its cleaved products with heat shock cognate protein 70 (Hsc70), a protein necessary for CMA or microautophagy. These findings suggest that KFERQ motif is important for normal processing and degradation of APP to preclude the accumulation of APP-CTFs although it may not be important for CMA or microautophagy.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.1
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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.

• BMB Reports
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• v.57 no.6
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.1
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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.

• Biomolecules & Therapeutics
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• v.27 no.3
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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.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.58-58
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• 2021

Although hypoxic/ischemic injury is thought to contribute to the incidence of Alzheimer disease (AD), the molecular mechanism that determines the relationship between hypoxia-induced β-amyloid (Aβ) generation and development of AD is not yet known. In this study, we investigated the protective effects of Acorus gramineus Soland. (AGS) on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced A β production in SH-SY5Y human neuroblastoma cells. Pretreatment of these cells with AGS significantly attenuated OGD/R-induced production of reactive oxygen species (ROS) and elevation of levels of malondialdehyde, nitrite (NO), prostaglandin E2 (PGE2), cytokines (TNF-α, IL-1β and IL-6) and glutathione, as well as superoxide dismutase activity. AGS also reduced OGD/R-induced expression of the apoptotic protein caspase-3, the apoptosis regulator Bcl-2, and the autophagy protein becn-1. Finally, AGS reduced OGD/R-induced Aβ production and cleavage of amyloid precursor protein, by inhibiting secretase activity and suppressing the autophagic pathway. Although supporting data from in vivo studies are required, our results indicate that AGS may prevent neuronal cell damage from OGD/R-induced toxicity.

• The Journal of Korean Physical Therapy
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• v.33 no.3
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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.

• Natural Product Sciences
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• v.26 no.3
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• pp.221-229
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• 2020

This study was undertaken to investigate the protective effect of rice bran oil (RBO) on amyloid β protein (Aβ) (25-35)-induced memory impairment and brain damage in an ICR mouse model. Memory impairment was produced by intracerebroventricular microinjection of 15 nmol Aβ (25-35) and assessed using the passive avoidance test. Treatment with RBO at 0.1, 0.5, or 1 mL/kg (p.o. daily for 8 days) protected against Aβ (25-35)-induced memory impairment. Furthermore, Aβ (25-35)-induced decreases in glutathione and increases in lipid peroxidation and cholinesterase activity in brain tissue were inhibited by RBO, and Aβ (25-35)-induced increases of phosphorylated mitogen-activated protein kinases (MAPKs) and inflammatory factors, and changes in the levels of apoptosis-related proteins were significantly inhibited by RBO. Furthermore, Aβ (25-35) suppressed the PI3K/Akt pathway and the phosphorylation of CREB, but increased phosphorylation of tau (p-tau) in mice brain; these effects were significantly inhibited by administration of RBO. These results suggest that RBO inhibits Aβ (25-35)-induced memory impairment by inducing anti-apoptotic and anti-inflammatory effects, promoting PI3K/Akt/CREB signaling, and thus, inhibiting p-tau formation.