• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.195-200
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• 2009

Zinc released from excited glutamatergic neurons accelerates amyloid ${\beta}$ (A ${\beta}$) aggregation, underscoring the therapeutic potential of zinc chelation for the treatment of Alzheimer's disease (AD). Zinc can also alter A ${\beta}$ concentration by affecting its degradation. In order to elucidate the possible role of zinc influx in secretase-processed A ${\beta}$ production, SH-SY5Y cells stably expressing amyloid precursor protein (APP) were treated with pyrrolidine dithiocarbamate (PDTC), a zinc ionophore, and the resultant changes in APP processing were examined. PDTC decreased A ${\beta}$ 40 and A ${\beta}$ 42 concentrations in culture media bathing APP-expressing SH-SY5Y cells. Measuring the levels of a series of C-terminal APP fragments generated by enzymatic cutting at different APP-cleavage sites showed that both ${\beta}$-and ${\alpha}$-cleavage of APP were inhibited by zinc influx. PDTC also interfered with the maturation of APP. PDTC, however, paradoxically increased the intracellular levels of A ${\beta}$ 40. These results indicate that inhibition of secretase-mediated APP cleavage accounts -at least in part- for zinc inhibition of A ${\beta}$ secretion.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.1
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• pp.57-62
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• 2013

Alzheimer's disease (AD), one of the most common forms of dementia, is characterized pathologically by the presence of intracellular neurofibrillary tangles and 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. Here, we show that MeOH extract from stem bark of Platycarya strobilacea Sieb. et. Zucc. (PSM) affects on the processing of APP from the APPswe over-expressing Neuro2a cell line. We found that PSM may regulate the processing of APP and increase the sAPP${\alpha}$. PSM does not change the protein level of presenilin and nicastrin, however, it reduces the protein expression level of BACE1. In addition, PSM reduces the secretion level of $A{\beta}42$ and $A{\beta}40$ from the cell line without toxicity. We suggest that Platycarya strobilacea may be useful as a herbal medicine to treat Alzheimer's disease.

• Fisheries and Aquatic Sciences
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• v.21 no.12
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• pp.38.1-38.9
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• 2018

Alzheimer's disease (AD) is a disturbing and advanced neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta ($A{\beta}$) and the hyperphosphorylation of tau proteins in the brain. The deposition of $A{\beta}$ aggregates triggers synaptic dysfunction, and neurodegeneration, which lead to cognitive disorders. Here, we found that FF isolated from an eatable perennial brown seaweed E.bicyclis protect against $A{\beta}$-induced neurotoxicity in neuroblastoma cells stably transfected with two amyloid precursor protein (APP) constructs: the APP695 cDNA (SH-SY5Y-APP695swe). The FF demonstrated strong inhibitory activity for ${\beta}$-secretase ($IC_{50}$ $16.1{\mu}M$) and its inhibition pattern was investigated using Lineweaver-Burk and Dixon plots, and found to be non-competitive. Then, we tested whether FF could inhibit production of $A{\beta}$ in SH-SY5Y-APP695swe. FF inhibited the production of $A{\beta}$ and soluble-APP, residue of APP from cleaved APP by ${\beta}$-secretase. Our data show that FF can inhibit the production of $A{\beta}$ and soluble-$APP{\beta}$ via inhibition of ${\beta}$-secretase activity. Taken together these results suggest that FF may be worthy of future study as an anti-AD treatment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.1
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• pp.91-95
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• 2010

Alzheimer's disease (AD) is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}$-amyloid (A${\beta}$) peptides. It is urgent to develop effective therapies for the treatment of AD, since our society rapidly accelerate aging. A${\beta}$ peptides have been believed to be neurotoxic and now are also considered to have affects on the mechanism of memory formation, which are generated by processing of amyloid precursor protein (APP). In this study, effects of Styrax Liquides (SL) on the metabolism of APP were analyzed. SL inhibited the secretion of A${\beta}$ from the Neuro2a cell line (APPswe cell) expressing a mutation of APPswe. Immunoblotting study showed that it inhibited ${\beta}$-site APP cleaving enzyme (BACE) from the APPswe cells. We suggest that SL inhibits APP metabolism and A${\beta}$ generation by the means of BACE inhibitory mechanism. This is the first report that SL inhibits the secretion of A${\beta}$ peptides from neuroblastoma cells.

• 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 Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.1037-1049
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• 2003

Numerous lines of evidence indicate that some of the neurotoxicity associated with Alzheimer's disease (AD) is due to proteolytic fragments of the amyloid precursor protein (APP). Most research has focused on the amyloid 6 (M). However, the possible role of other cleaved products of APP is less clear. Lately It has been reported that a recombinant carboxy-terminal 105 amino acid fragment (CT105) of APP induced strong nonselective inward currents in Xenopus oocyte. In a brain with Alzheimer's disease (AD), to investigate the roles of carboxyl-terminal fragment (CT105) of amyloid precursor protein (APP) in apoptosis processes possibly linked to neurodegeneration associated with AD, we examined the effects of the CT of APP with 105 amino acid residues (CT105) on the alteration of apoptosis triggers in neubroblastoma cells. We have investigated whether Radix Polygalae and Rhizoma Acori Graminei mixture extract (RP+RAG) inhibits CT105-induced apoptosis of neuroblastoma cells. We found that RP+RAG inhibits CT105-induced apoptosis in SK-N-SH cells. Treatment of the cells with RP+RAG inhibited CT105-induced DNA fragmentation and Tunel assay of nuclear chromatin and inhibited the caspase-3 expression in SK-N-SH cells. As the result of this study, In RP+RAG group, the apoptosis in the nervous system is inhibited, the repair against the degerneration of neuroblastoma cells by CT105 expression is promoted. These results indicate that RP+RAG possess strong inhibitory effect of apoptosis in the nervous system and repair effect against the degeneration of neuroblastoma cells by CT105 expression

• 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.

• Nutrition Research and Practice
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• v.8 no.4
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• pp.386-390
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• 2014

BACKGROUND: Acanthopanax divaricatus var. albeofructus (ADA) extract has been reported to have anti-oxidant, immunomodulatory, and anti-mutagenic activity. MATERIALS/METHODS: We investigated the effects of ADA extract on two mouse models of Alzheimer's disease (AD); intracerebroventricular injection of ${\beta}$-amyloid peptide ($A{\beta}$) and amyloid precursor protein/presenilin 1 (APP/PS1)-transgenic mice. RESULTS: Intra-gastric administration of ADA stem extract (0.25 g/kg, every 12 hrs started from one day prior to injection of $A{\beta}1$-42 until evaluation) effectively blocked $A{\beta}1$-42-induced impairment in passive avoidance performance, and $A{\beta}1$-42-induced increase in immunoreactivities of glial fibrillary acidic protein and interleukin (IL)-$1{\alpha}$ in the hippocampus. In addition, it alleviated the $A{\beta}1$-42-induced decrease in acetylcholine and increase in malondialdehyde levels in the cortex. In APP/PS1-transgenic mice, chronic oral administration of ADA stem extract (0.1 or 0.5 g/kg/day for six months from the age of six to 12 months) resulted in significantly enhanced performance of the novel-object recognition task, and reduced amyloid deposition and IL-$1{\beta}$ in the brain. CONCLUSIONS: The results of this study suggest that ADA stem extract may be useful for prevention and 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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2005.04a
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• pp.35-40
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• 2005