• Korean Journal of Biological Psychiatry
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• v.3 no.2
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• pp.170-180
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• 1996

Lowered immune function in the senile dementia patients may be related to the abnormal metabolism of amyloid precursor protein(APP). To investigate the passibility of an abnormal metabolism of APP in lymphocytes and the possible role of APP in the activation of lymphocytes in senile dementia patients, immunohistochemical study of rat spleen and fluorescence activated cell sorter analysis(FACS) of human lymphocytes with the specific antigen far each lymphocyte and double fluorescent marker with antibody to APP were performed. After stimulating lymphocyte with phytohemagglutinin(PHA), APP mRNA and protein were extracted and quantitfied and the influence of ${\beta}$-amyloid protein($A{\beta}$) specific antibody on lymphocyte division was investigated. In spleen, the majority of cells showing $A{\beta}$ immunoreactivity was found in the T-sell dependent zone. FACS indicated that around 90% $CD_4(+)$ T-cells and 60% of $CD_8(+)$ T-sell were immunoreactive to $A{\beta}$ specific antibody(mAb 4G8). Northern blot analysis shows that lymphocyte APP mRNA was gradually increased to reach a maximum at 3 days after activation with lectin mitogen PHA. However, the $A{\beta}$ immunoreactivity an cell surface remained constant during stimulation with PHA, indicating that the release of APP(secreted farm of APP) might be increased. A very large increase in soluble APP secretion was observed in T-lymphocyte upon activation, but only law levels in the resting stale. Immunoblot was carried out an the protein obtained from cell lysate after stimulating lymphocyte by applying PHA to the cultured lymphocyte, and the result was that $A{\beta}$ band of immature farm under 116 KDa marker decreased as the duration of culture was increased after PHA stimulation. The monoclonal $A{\beta}$ specific(4G8) and polyclonal APP antibodies did not inhibit the [$^3H$]-thymidine uptake of mitogen-treated lymphocytes significantly, suggesting that mitogenesis can not be inhibited by specific $A{\beta}$ and polyclonal APP antibody. These results suggest that APP is expressed in T-cell and might be closely associated with the function of T-cells.

• Toxicological Research
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• v.29 no.4
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• pp.235-240
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• 2013

Extracellular accumulation of amyloid beta protein ($A{\beta}$) plays a central role in Alzheimer's disease (AD). Some metals, such as copper, lead, and aluminum can affect the $A{\beta}$ accumulation in the brain. However, the effect of mercury on $A{\beta}$ accumulation in the brain is not clear. Thus, this study was proposed to estimate whether mercury concentration affects $A{\beta}$ accumulation in PC12 cells. We treated 10, 100, and 1000 nM $HgCl_2$ (Hg) or $CH_3HgCl_2$ (MeHg) for 48 hr in PC12 cells. After treatment, $A{\beta}_{40}$ in culture medium increased in a dose- and time-dependent manner. Hg and MeHg increased amyloid precursor protein (APP), which is related to $A{\beta}$ production. Neprilysin (NEP) levels in PC12 cells were decreased by Hg and MeHg treatment. These results suggested that Hg induced $A{\beta}$ accumulation through APP overproduction and reduction of NEP.

• 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.

• Korean Journal of Pharmacognosy
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• v.46 no.4
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• pp.327-333
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• 2015

Alzheimer's disease (AD) is a progressive neurodegenerative disorder symptomatically characterized by impairment in memory and cognitive abilities. AD is characterized pathologically by the deposition of ${\beta}$-amyloid ($A{\beta}$) peptides of 40-42 residues, which are generated by processing of amyloid precursor protein (APP). $A{\beta}$ has been believed to be neurotoxic and now is also considered to have a role on the mechanism of memory dysfunction. In this study, we tested that EtOH extract of the fruits of Chaenomeles sinensis Koehne (CSE) affects on the processing of APP from the APPswe over-expressing Neuro2a cell line. We found that CSE increased over 2 folds of the $sAPP{\alpha}$ secretion level, a metabolite of ${\alpha}$-secretase. We showed that CSE reduced the secretion level of $A{\beta}42$ and $A{\beta}40$ by down regulation of ${\beta}$-secretase (BACE) without cytotoxicity. Furthermore, we found that CSE inhibited BACE and acetylcholinesterase activity in vitro. We suggest that Chaenomelis Fructus may be an useful source to develop a herbal medicine for AD.

• 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.7
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• pp.376-381
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• 2016

Several lines of evidence have revealed that phosphorylation of amyloid precursor protein (APP) at Thr668 is involved in the pathogenesis of Alzheimer's disease (AD). Okadaic acid (OA), a protein phosphatase-2A inhibitor, has been used in AD research models to increase tau phosphorylation and induce neuronal death. We previously showed that OA increased levels of APP and induced accumulation of APP in axonal swellings. In this study, we found that in OA-treated neurons, phosphorylation of APP at Thr668 increased and accumulated in axonal swellings by c-jun N-terminal kinase (JNK), and not by Cdk5 or ERK/MAPK. These results suggest that JNK may be one of therapeutic targets for the treatment of AD.

• Journal of the Korean Magnetic Resonance Society
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• v.8 no.1
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• pp.19-27
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• 2004

C-terminal fragments of APP (APP-CTs), that contain complete Abeta sequence, are found in neuritic plaques, neurofibrillary tangles and the cytosol of lymphoblastoid cells obtained from AD patients. CT16, Lys649-Asp664 (KKQYTSIHHGVVEVD) has been known as the most toxic part in the C-terminal fragment of amyloid precursor protein (APP). The solution structure of CT16 was investigated using NMR spectroscopy in various membrane-mimicking environments. According to Circular Dichroim (CD) spectra, CT16 has a random structure in aqueous solution, while conformational change was induced by addition of TFE and SDS micelle. Tertiary structure as determined by NMR spectroscopy shows that CT16 has a ${\beta}$-turn conformation in trifluoroethanol-containing aqueous solution.

• Development and Reproduction
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• v.21 no.4
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• pp.417-424
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• 2017

Alzheimer's disease (AD) is neurodegenerative disease, characterized by the progressive decline of memory, cognitive functions, and changes in personality. The major pathological features in postmortem brains are neurofibrillary tangles and amyloid beta ($A{\beta}$) deposits. The majority of AD cases are sporadic and age-related. Although AD pathogenesis has not been established, aging and declining mitochondrial function has been associated. Mitochondrial dysfunction has been observed in AD patients' brains and AD mice models, and the mice with a genetic defect in mitochondrial complex I showed enhanced $A{\beta}$ level in vivo. To elucidate the role of mitochondrial complex I in AD, we used SH-SY5Y cells transfected with DNA constructs expressing human amyloid precursor protein (APP) or human Swedish APP mutant (APP-swe). The expression of APP-swe increased the level of $A{\beta}$ protein in comparison with control. When complex I was inhibited by rotenone, the increase of ROS level was remarkably higher in the cells overexpressing APP-swe compared to control. The number of dead cell was significantly increased in APP-swe-expressing cells by complex I inhibition. We suggest that complex I dysfunction accelerate amyloid toxicity and mitochondrial complex I dysfunction in aging may contribute to the pathogenesis of sporadic AD.

• Korean Journal of Pharmacognosy
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• v.53 no.2
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• pp.102-110
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• 2022

Alzheimer's disease (AD) is the most common form of dementia, and the accumulation of β-amyloid (Aβ) in the brain triggers AD, followed by hyperphosphorylation of tau protein, neurofibrillary tangles, and synapses loss, neuronal cell death, and cognitive decline occur in a chain. In APPswe neuronal cell line, 50 ㎍/ml of Campbell early (Vitis labruscana B.) leaves 50% ethanol extract (VLL) treatment inhibited the secretion of Aβ1-42 by about 63% and the secretion of Aβ1-40 by about 50%. VLL did not target the enzymatic activity of the amyloidogenic pathway and decreased the protein expression of APP. As a result of RT-qPCR (Reverse transcription-quantitative real-time PCR) of the APPswe cell line treated with VLL, it is thought that the protein expression of APP was reduced by inhibiting the transcription process of the APP gene. In addition, VLL inhibited acetylcholinesterase (AChE) enzyme activity in vitro by 27.6% and 54.7%, respectively, at 50 and 100 ㎍/ml concentrations. We found that VLL inhibited the production of Aβ, a dementia-inducing substance, by suppressing the transcription of the APP gene, and that VLL inhibited AChE activity. We suggest that VLL has the potential as a natural drug material that modulates the alleviation of dementia symptoms.

• 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.