• Ocean and Polar Research
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• 제39권1호
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• pp.45-49
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• 2017

During the search for anticholinesterase compounds from marine organisms, we were able to isolate 6,6'-bieckol from a red alga, Grateloupia elliptica. This compound showed moderate acetylcholinesterase (AChE) inhibitory activity in a micromole range ($IC_{50}$ $44.5{\mu}M$). However, for butyrylcholinesterase (BuChE), a new target for the treatment of Alzheimer's disease (AD), it showed particularly potent inhibitory activity ($IC_{50}$ $27.4{\mu}M$), which is more potent compared to AChE. It also inhibits BACE-1, a new target for reducing the generation of ${\beta}-amyloid$.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.271.2-271.2
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• 2003

The ${\gamma}$- and ${\beta}$-secretase are one of the most important proteases, which cleave amyloid precursor protein (APP) into neurotoxic A${\beta}$ peptide in Azheimer's type dementia. In the course of screening for anti-dementia agents from natural products, the mycelial culture of mushroom Phellinus linteus showed potent inhibition againt ${\beta}$-secretase (BACE1). (omitted)

• 건축사
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• 통권580호
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• pp.22-35
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• 2017

• Journal of Microbiology
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• 제44권6호
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• pp.665-670
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• 2006

Amyloid $\beta$-peptide (A$\beta$), which is a product of the proteolytic effect of $\beta$-secretase (BACE) on an amyloid precursor protein, is closely associated with Alzheimer's disease (AD) pathogenesis. There is sufficient evidence to suggest that a BACE inhibitor may reduce A$\beta$ levels, thus decreasing the risk of AD. In a previous study, an extract of Clavicorona pyxidata DGUM 29005 mycelia was found to inhibit the production of a soluble $\beta$-amyloid precursor protein (s$\beta$APP), A$\beta$, and BACE in neuronal cell lines. We sought to determine whether this mycelial extract exerts the same effect in human rhabdomyosarcoma A-204 and rat pheochromocytoma PC-12 cells. We found that the production of A$\beta$ decreased in a dose-dependent manner in the presence of the mycelial extract and that the concentration of A$\beta$ never exceeded $50{\mu}g/ml$. The presence of sAPP was detected in every culture medium to which the mycelial extract had been added and its concentration remained the same, regardless of the concentration of the extract used. Endogenous $\beta$-secretase activity in A-204 and PC-12 cellular homogenates also decreased in the presence of this extract. These cells, in culture, were not susceptible to the cytotoxic activity of the mycelial extract.

• Archives of Pharmacal Research
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• 제28권12호
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• pp.1328-1332
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• 2005

In the course of screening for anti-dementia agents from natural products, two $\beta$-secretase (BACE1) inhibitors were isolated from the husk of pomegranate (Punica granatum) by activity-guided purification. They were identified as ellagic acid and punicalagin with $IC_{50}$ values of 3.9 $\times$$10^{-6}$ and 4.1$\times$$10^{-7}$ M and Ki values of 2.4$\times$$10^{-5}$and 5.9$\times$$10^{-7}$ M, respectively. The compounds were non-competitive inhibitors with a substrate in the Dixon plot. Ellagic acid and punicalagin were less inhibitory to $\alpha$-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, thus indicating that they were relatively specific inhibitors of BACE1.

• 대한본초학회지
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• 제29권6호
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• pp.73-83
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• 2014

Objectives : This study was investigated the effects of the root of Polygala tenuifolia (POL) on learning and memory impairment induced by chronic cerebral hypoperfusion in rats. Methods : Chronic cerebral hypoperfusion was produced by permanent bilateral common carotid artery occlusion (pBCAO). POL was administered orally once a day (130 mg/kg of water-extract) for 28 days starting at 4 weeks after the pBCAO. The acquisition of learning and the retention of memory were tested on 9th week after the pBCAO using the Morris water maze. In addition, effects of POL on $A{\beta}$ generation and expressions of APP and BACE1 were observed in the hippocampus of rats. Results : POL significantly prolonged the swimming time spent in target quadrant and significantly reduced the swimming time spent in the quadrant far from the target. POL significantly increased the percentage of swim in the targer quadrant in the retention test, while POL was not effective on the escape latencies in the acquisition training trials. POL significantly reduced the levels of $A{\beta}_{(1-40)}$ and $A{\beta}_{(1-42)}$ in the cerebral cortex and the level of $A{\beta}_{(1-42)}$ in the hippocampus produced by chronic cerebral hypoperfusion. POL also significantly attenuated the up-regulation of APP and BACE1 expression in the hippocampus produced by chronic cerebral hypoperfusion. Conclusions : The results show that POL alleviated memory deficit and up-regulation of $A{\beta}$ and BACE1 expressions in the hippocampus. This result suggests that POL may exert ameliorating effect on memory deficit through inhibition of ${\beta}$-secretase activity and $A{\beta}$ generation.

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2006년도 Spring Conference
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• pp.93-105
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• 2006

P25/CDK5 phosphorylates BACE1. 2. P25 is a new target for AD therapeutics. 3. P25 inhibitors should block both $A{\beta}$ pathway and Tau pathway.

• 동의생리병리학회지
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• 제27권1호
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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.

• Bulletin of the Korean Chemical Society
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• 제27권8호
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• pp.1211-1218
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• 2006

The enantiomerically pure (2R,3S)- and (2R,3R)-3-amino-2-hydroxy-4-phenylbutanoic acids (AHPBA) 1 and 3 are readily obtained from D-glucono-a-lactone. Both AHPBAs are the structural key units of KMI derivatives which are the potent inhibitors of BACE 1 ($\beta$-secretase) and HIV protease. Additionally, the obtained AHPBAs 1 and 3 are converted to dipeptides of bestatin stereoisomers 2 and 4.

• 동의생리병리학회지
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• 제30권1호
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• pp.33-39
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• 2016

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 β-amyloid(Aβ) peptides of 40-42 residues. Aβ has been believed to be neurotoxic and now is also considered to have a role on the mechanism of memory dysfunction. Only a few acetylcholinesterase(AChE) inhibitors have been developed for treatment of AD, although the numbers of patients are rapidly increasing within aging society. Here, we show that ethanol extract of Rosae Rugosae Flos(RR) or its butanol fraction reduce the enzyme activity of AChE and BACE1(β-site APP cleaving enzyme 1). Furthermore, We found that RR inhibits Aβ aggregation and removes Aβ aggregates by Transmission electron microscopy(TEM). In addition, RR reduces the free radical of 2, 2-diphenyl-1-picrylhydrazyl(DPPH). We suggest that Rosae Rugosae Flos may be useful as a herbal medicine to treat AD.