• Journal of Oriental Neuropsychiatry
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• v.11 no.1
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• pp.19-36
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• 2000

Alzheimer's disease (AD) is progressive neurodegenerative disease, which is pathologically characterized by neuritic plaques and neurofibrillary tangles associated with the acetylcholinesterase, apolipoprotein E and butylcholinesterase, and by mutations in the presenilin genes PS1 and PS2, and amyloid precursor proteins (APPs) overexpression. The present research is to examine the inhibition effect of KBT on PS1, PS2 and APPs overexpression by detected to Western blotting. To verify the Effects of KBT on cognitive deficits further, we tested it on the scopolamine (1 mg/kg)-induced amnesia model of the mice using the Morris water maze tests, and there was ameliorative effects of memory impairment as a protection to scopolamine. KBT only partially blocked the increase in blood serum level of acetylcholinesterase and Uric acid induced by scopolamine, whereas blood glucose level was shown to attenuate the amnesia induced by scopolamine and inreased extracellular serum level compared with only scopolamine injection. In conclusion, studies of KBT that has been know as anti-choline and inhibition ablilities of APPs overexpression, this could also be used further as a important research data for a preventive and promising symptomatic treatment for Alzheimer's disease.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.1
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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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2006.04a
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• pp.123-135
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• 2006

Alzheimer's disease (AD) is the most common form of dementia in the aging population and is clinically characterized by a progressive loss of cognitive abilities. Pathologically, it is defined by the appearance of senile plaques - extracellular insoluble, congophilic protein aggregates composed of amyloid $\beta$ (A$\beta$) and neurofibrillary tangles (NFTs) - inyracellular lesions consisting of paired helical filaments from hyperphosphorylated cytoskeletal tau protein as described by Alois Alzheimer a century ago. These hallmarks still serve as the major criteria for a definite diagnosis of the disease. Consequently, one of the key strategy for drug development in this disease area focuses on reducing the concentration of cerebral A$\beta$ plaque by using substances that inhibit A$\beta$ fibril formation. We focused on developing inhibitors by synthesizing several kinds of aromatic molecules. The synthetic compounds were initially screened to evaluate the effective compound by tioflavin T fluorescence assay. The selected effective compounds were tested cytotoxicity and protective effect from A$\beta$-induced neuronal toxicity by cell based MTT assay with HT22 hippocampal neurons. The BBB permeability on effectors was also tested in in vitro co-culture model(HUVEC/C6 cell line). The behavior test wea carried out in mutant APP/PS1 transgenic mouse model of Alzheimer's disease. And inhibition of A$\beta$ fibril formation by the effective compound was monitored with transmitted electron microscopic images.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2006.04a
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• pp.109-120
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• 2006

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. The pathological hallmarks of AD are senile plaques and neurofibrillary tangles in the brain. Major component of senile plaques is amyloid beta peptide(A$\beta$) which is derived from amyloid precursor protein (APP). A$\beta$ is generated through the sequential cleavage of App by $\beta$ - and $\gamma$-secretases. $\beta$-secretase excises the ectodomain of APP ($\beta$-APPs) to leave a 99-amino acid long C-terminal fragment (APP-C99-CTF) in the membrane. $\gamma$-secretase then cleaves this membrane-tethered APP-CTF within the transmembrane domain, so releasing A$\beta$ peptides and APP-intracellular domain (AICD). Thus, $\beta$- and $\gamma$-secretase are regarded to perform the key steps in the pathogenesis of AD and have become important therapeutic targets in the prevention and treatment of AD. Enormous efforts have been focused to develop the amyloid beta related drug for cure of AD becuase A$\beta$ is believed to be one of the major causes of AD. since major pharmaceutical companies in world wide base compete to develop new drug for AD, we have to be careful to choose the drug target to success the tough race. In the present talk, possible drug targets based on basic research results will be discussed. These molecules should be a good target for development of new drug for AD and be less competitive to have a good shape for world wide competition.

• Journal of Oriental Neuropsychiatry
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• v.12 no.1
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• pp.151-167
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• 2001

Alzheimer's disease(AD) is a progressive neurodegenerative disease, which is pathologically characterized by neuritic plaques and neurofibrillary tangles associated with the acetylchohnesterase, apolipoprotein E and butylcholinesterase, and by mutations in the presenilin genes PS1 and PS2, and amyloid precursor proteins (APPs)'s overexpression. The present research is to examine the inhibition effect of BYCNT on PS-1, PS-2 and APPs's overexpression by detected to Western blotting. To verify the effects of BYCNT on cognitive deficits further, we tested it on the scopolamine(1mg/kg)-induced amnesia model of the mice using the Morris water maze tests, and there was ameliorative effects of memory impairment as a protection from scopolamine. BYCNT only partially blocked the increase in blood serum level of acetylcholinesterase and Uric acid induced by scopolamine, whereas blood glucose level was shown to attenuate the amnesia induced by scopolamine and inreased extracellular serum level compared with only scopolamine injection. In conclusion, studies of BYCNT that has been known as anti-choline and inhibition ablilities of APPs overexpression, this could also be used further as a important research data for a preventive and promising symptomatic treatment for Alzheimer's disease.

• 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.1
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• pp.72-77
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• 2015

One of the most common forms of dementia, Alzheimer's disease (AD) is a progressive neurodegenerative disorder symptomatically characterized by impairment in memory and cognitive abilities. AD is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}$-amyloid ($A{\beta}$) peptides, 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 MeOH extract of Impatiens balsamina L. (IBM) affects on the processing of APP from the APPswe over-expressing Neuro2a cell line. We found that IBM increased over 2 folds of the $sAPP{\alpha}$ secretion level, a main metabolite of ${\alpha}$-secretase. We shown that IBM reduced the secretion level of $A{\beta}42$ and $A{\beta}40$ without cytotoxicity. BACE (${\beta}$-site APP cleaving enzyme) FRET assay shown that BACE activity was specifically decreased in the presence of IBM. We suggest that Impatiens balsamina L. may be an useful source to develop a herbal medicine of BACE inhibitor for Alzheimer's disease.

• Bulletin of the Korean Chemical Society
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• v.26 no.8
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• pp.1225-1228
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• 2005

C-terminal fragments of APP (APP-CTs), that contain A$\beta$ sequence, are found in neurotic plaques, neurofibrillary tangles and the cytosol of lymphoblastoid cells obtained from AD patients. CT26, Thr639-Asp664 (TVIVITLVMLKKKQYTSIHH GVVEVD) includes not only the transmembrane domain but also the cytoplasmic domain of APP. This sequence is produced from cleavage of APP by caspase and $\gamma$-secretase. In this study, the solution structure of CT26 was investigated using NMR spectroscopy and circular dichroism (CD) spectropolarimeter in various membrane-mimicking environments. According to CD spectra and the tertiary structure of CT26 determined in TFE-containing aqueous solution, CT26 has an α-helical structure from $Val^{2}\;to\;Lys^{11}$ in TFE-containing aqueous solution. However, according to CD data, CT26 adopts a $\beta$-sheet structure in the SDS micelles and DPC micelles. This result implies that CT26 may have a conformational transition between $\alpha$-helix and $\beta$-sheet structure. This study may provide an insight into the conformational basis of the pathological activity of the C-terminal fragments of APP in the model membrane.

• BMB Reports
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• v.53 no.1
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• pp.10-19
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• 2020

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The AD pathophysiology entails chronic inflammation involving innate immune cells including microglia, astrocytes, and other peripheral blood cells. Inflammatory mediators such as cytokines and complements are also linked to AD pathogenesis. Despite increasing evidence supporting the association between abnormal inflammation and AD, no well-established inflammatory biomarkers are currently available for AD. Since many reports have shown that abnormal inflammation precedes the outbreak of the disease, non-invasive and readily available peripheral inflammatory biomarkers should be considered as possible biomarkers for early diagnosis of AD. In this minireview, we introduce the peripheral biomarker candidates related to abnormal inflammation in AD and discuss their possible molecular mechanisms. Furthermore, we also summarize the current state of inflammatory biomarker research in clinical practice and molecular diagnostics. We believe this review will provide new insights into biomarker candidates for the early diagnosis of AD with systemic relevance to inflammation during AD pathogenesis.

• Korean Journal of Clinical Laboratory Science
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• v.38 no.3
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• pp.179-183
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• 2006

Alzheimer's disease (AD) is characterised neuropathologically by the accumulation of neuritic plaques and neurofibrillary tangles as well as by cerebrovascular amyloid deposition and neuronal cell loss. Current advances have shown the apolipoproteinE-epsilon 4 (ApoE4) allele to be highly associated with late-onset familial and sporadic Alzheimer's disease (AD) in Western populations. The association of ApoE allele frequencies and dementia remains unknown in populations from many countries. We recently initiated a project to examine ApoE frequencies in non-demented healthy Koreans. Genomic DNA in hair root from a thousand persons was collected and ApoE gene type was investigated with the methods of polymerase chain reaction (PCR) and restriction fragment length polymorphism. A group of a thousand non-demented Koreans over the age of 40 years were found to be positive in 15.7% of the cases for ApoE4. AD and ApoE4 were closely related. ApoE epsilon 4 was a dangerous factor of AD and ApoE 4 allele made a contribution to the heterogenicity of AD.