• Nutrition Research and Practice
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• v.13 no.1
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• pp.64-69
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• 2019

BACKGROUND/OBJECTIVES: Alzheimer's disease is a neurodegenerative disease that induces symptoms such as a decrease in motor function and cognitive impairment. Increases in the aggregation and deposition of amyloid beta protein ($A{\beta}$) in the brain may be closely correlated with the development of Alzheimer's disease. In this study, the effects of an adzuki bean extract on the aggregation of $A{\beta}$ were examined; moreover, the anti-Alzheimer's activity of the adzuki extract was examined. MATERIALS/METHODS: First, we undertook thioflavin T (ThT) fluorescence analysis and transmission electron microscopy (TEM) to evaluate the effect of an adzuki bean extract on $A{\beta}_{42}$ aggregation. To evaluate the effects of the adzuki extract on the symptoms of Alzheimer's disease in vivo, $A{\beta}_{42}$-overexpressing Drosophila were used. In these flies, overexpression of $A{\beta}_{42}$ induced the formation of $A{\beta}_{42}$ aggregates in the brain, decreased motor function, and resulted in cognitive impairment. RESULTS: Based on the results obtained by ThT fluorescence assays and TEM, the adzuki bean extract inhibited the formation of $A{\beta}_{42}$ aggregates in a concentration-dependent manner. When $A{\beta}_{42}$-overexpressing flies were fed regular medium containing adzuki extract, the $A{\beta}_{42}$ level in the brain was significantly lower than that in the group fed regular medium only. Furthermore, suppression of the decrease in motor function, suppression of cognitive impairment, and improvement in lifespan were observed in $A{\beta}_{42}$-overexpressing flies fed regular medium with adzuki extract. CONCLUSIONS: The results reveal the delaying effects of an adzuki bean extract on the progression of Alzheimer's disease and provide useful information for identifying novel prevention treatments for Alzheimer's disease.

• 한국약용작물학회:학술대회논문집
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• 2011.09a
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• pp.31-45
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• 2011

The amyloid ${\beta}$-peptide ($A{\beta}$), which originates from the proteolytic cleavage of amyloid precursor protein (APP), plays a central role in the pathogenesis of Alzheimer's disease (AD). Mounting evidence indicates that different species of $A{\beta}$, such as $A{\beta}$ oligomers and fibrils, may contribute to AD pathogenesis via distinct mechanisms at different stages of the disease. Importantly, elevation and accumulation of soluble $A{\beta}$ oligomers closely correlate with cognitive decline and/or disease progression in animal models of AD. In agreement with these studies, oligomers of $A{\beta}$ have been shown to directly affect synaptic plasticity, a neuronal process that is known to be essential for memory formation. Our previous studies showed that $A{\beta}$ induces the breakdown of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a phospholipid that regulates key aspects of neuronal function. PI(4,5)P2 breakdown was found to be a key step toward synaptic and memory dysfunction in a mouse model of AD. To this end, we seek to identify small molecules that could elevate the levels of PI(4,5)P2 and subsequently block $A{\beta}$ oligomer-induced breakdown of PI(4,5)P2 and synaptic dysfunction.. We found that (20S)Rg3, an active triterpene glycoside from heat-processed ginseng, serves as an agonist for phosphatidylinositol 4-kinase IIalpha (PI4KIIalpha), which is a lipid kinase that mediates a rate-limiting step in PI(4,5)P2 synthesis. Consequently, (20S)Rg3 stimulates PI(4,5)P2 synthesis by directly stimulating the activity of PI4KIIalpha. Interestingly, treatment of a mouse model of AD with (20S)Rg3 leads to reversal of memory deficits. Our data suggest that the PI(4,5)P2-promoting effects of (20S)Rg3 may help mitigate the cognitive symptoms associated with AD.

• BMB Reports
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• v.43 no.10
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• pp.704-709
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• 2010

The Swedish mutation (K595N/M596L) of amyloid precursor protein (APP-swe) has been known to increase abnormal cleavage of cellular APP by Beta-secretase (BACE), which causes tau protein hyperphosphorylation and early-onset Alzheimer's disease (AD). Here, we analyzed the effect of APP-swe in global gene expression using deep transcriptome sequencing technique. We found 283 genes were down-regulated and 348 genes were up-regulated in APP-swe expressing H4-swe cells compared to H4 wild-type cells from a total of approximately 74 million reads of 38 base pairs from each transcriptome. Two independent mechanisms such as kinase and phosphatase signaling cascades leading hyperphosphorylation of tau protein were regulated by the expression of APP-swe. Expressions of catalytic subunit as well as several regulatory subunits of protein phosphatases 2A were decreased. In contrast, expressions of tau-phosphorylating glycogen synthase kinase $3\beta$(GSK-3$\beta$), cyclin dependent kinase 5 (CDK5), and cAMP-dependent protein kinase A (PKA) catalytic subunit were increased. Moreover, the expression of AD-related Aquaporin 1 and presenilin 2 expression was regulated by APP-swe. Taken together, we propose that the expression of APP-swe modulates global gene expression directed to AD pathogenesis.

• Applied Microscopy
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• v.42 no.4
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• pp.179-185
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• 2012

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Neuropathological hallmarks of AD are amyloid plaques, dystrophic neurite, and alteration of subcellular organelles. However, the morpho-functional study of this degenerative process and ultimate neuronal death remains poorly elucidated. In this study, immunohistochemical and ultrastructural analyses were performed to clarify the abnormal morphological alterations caused by the progression of AD in APP/PSEN1 transgenic mice, express human amyloid precursor protein, as a model for AD. In transgenic AD mice brain, the accumulation of Amyloid ${\beta}$ plaques and well-developed dystrophic neurites containing anti-LC3 antibody-positive autophagosomes were detected in the hippocampus and cortex regions. We also found severe disruption of mitochondrial cristae using high-voltage electron microscopy and three-dimensional electron tomography (3D tomography). These results provide morpho-functional evidence on the alteration of subcellular organelles in AD and may help in the investigation of the pathogenesis of AD.

• Journal of Microbiology and Biotechnology
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• v.19 no.9
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• pp.960-965
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• 2009

${\beta}2$-Microglobulin (${\beta}2m$) is known to be a major factor for dialysis-related amyloidosis. We have studied ${\beta}2m$ removal through an aggregation process, which was initiated by a ligand that could catch the ${\beta}2m$ monomer and promote its aggregation into fibril. As a ligand, we have prepared ${\beta}2m$ fibril fragments and used them as a seed. The seed was coupled to PEGylated-PS beads to remove the monomeric ${\beta}2m$ from solution. The ${\beta}2m$ seed-conjugated resin effectively adsorbed the ${\beta}2m$ monomers with a capacity of 3.6 mg/ml via promoting their aggregation into fibrils on the resin at pH 7.4.

• The Korea Journal of Herbology
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• v.30 no.1
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• pp.67-75
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• 2015

Objectives : The aim of this study is to examine the neuroprotective effect of wheat bran extract (WBE) against ${\beta}$-amyloid ($A{\beta}$)-induced apoptotic cell death in SH-SY5Y human neuroblastoma cells and memory impairment in triple transgenic animal model's of Alzheimer's disease (3xTg AD mice). Methods : In SH-SY5Y cells, MTT assay and TUNEL staining were conducted to evaluate the protective effect of WBE against $A{\beta}_{25-35}$-induced neurotoxicity and apoptosis. Alterations in mitochondrial transmembrane potential (MMP), expression of proapoptotic Bax and antiapoptotic Bcl-2 proteins, cleavage of PARP, and brain-derived neurotrophic factor (BDNF) levels were analyzed to elucidate the neuroprotective mechanism of WBE. To further investigate the memory enhancing effect of WBE, Morris water maze test was performed in 3xTg AD mice. Results : In SH-SY5Y cells, WBE protected against $A{\beta}_{25-35}$-caused cytotoxicity and apoptosis as shown by the restoration of cell viability in MTT assay and inhibition of DNA fragmentation in TUNEL staining. $A{\beta}_{25-35}$-induced apoptotic signals such as dissipation of MMP, decreased Bcl-2/Bax ratio, and cleavage of PARP were suppressed by WBE. Moreover, WBE up-regulated the protein levels of BDNF, which seemed to be mediated by activation of cAMP response element-binding protein (CREB). In 3xTg AD mice, oral administration of WBE attenuated learning and memory deficit as verified by reduced mean escape latency in water maze test. Conclusions : WBE protects neuronal cells from $A{\beta}_{25-35}$-induced apoptotic cell death and restores learning and memory impairments in 3xTg AD mice. These findings suggest that WBE exhibit neuroprotective potential for the management of AD.

• Biomolecules & Therapeutics
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• v.23 no.2
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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.

• Journal of the Korean Magnetic Resonance Society
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• v.15 no.2
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• pp.175-186
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• 2011

Amyloid fibrils have long been known to be the well known ${\alpha}$-helix to ${\beta}$-sheet transition characterizing the conversion of cellular to scrapie forms of the prion protein. A very short sequence of Yeast prion-like protein, GNNQQNY (SupN), is responsible for aggregation that induces diseases. KSI-fused tandem repeats of SupN vector are constructed and used to express SupN peptide in Escherichia coli (E.Coli). A method for a production, purification, and cleavage of tandem repeats of recombinant isotopically enriched SupN in E. coli is described. This method yields as much as 20 mg/L of isotope-enriched fusion proteins in minimal media. Synthetic SupN peptides and $^{13}C$ Gly labeled SupN peptides are studied by Congo Red staining, Birefringence and transmission electron microscopy to characterize amyloid fibril formation. To get a better understanding of aggregation-structure relationship of 7 residues of Yeast prion-like protein, the change of a conformational structure will be studied by $^{13}C$ solid-state nmr spectroscopy as powder of both amorphous and fibrillar forms.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.208.1-208.1
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• 2003

In recent, growing aged people in coupled with the increased senile dementia, Alzheimer's disease, has been a social interests to be cleared out. Alzheimer Disease(AD), first reported by Alios Alzheimer (1864-1915) in 1907, is a neurodegenrative disease. Nothing exact cause of AD is available by now, but in clinical founding ${\beta}$-amyloid peptide(A${\beta}$) and microtubule associated protein($\tau$ protein) is to involved in the disease, and the most important feature in AD is Known to induce chronic inflammation to neuron cell. (omitted)

• Biomolecules & Therapeutics
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• v.14 no.2
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• pp.96-101
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• 2006

Amyloid$\beta(A{\beta})$ has been reported have an effect on the induction of oxidative stress that involves the functional and structural abnormalities in Alzheimer's disease. As a role of a radical scavenger, a green tea treatment was found have some inhibitory effect on the neurodegenerative process. The aim of this study was to determine if green tea catechin (GTC) reduces in transgenic model. To test this, transgenic mice carrying neuronspecific enolase (NSE) controlled C-terminus (105) of APP (APP-C105) were created and treated them with a low ana high dose of GTC for 6 months. Herein, we conclude that transgenic mice expressing NSE/APP-C105 were successfully created and the GTC-treated group exhibited significant reduction in body weight. Thus, GTC might be a good prevention of obesity or good treatment for AD patient.