• Proceeding of EDISON Challenge
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• 2015.03a
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• pp.14-23
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• 2015

Alzheimer's disease is one of the most common types of degenerative dementia. As a considerable cause of Alzheimer's disease, neurotoxic plaques composed of 39 to 42 residue-long amyloid beta($A{\beta}$) fibrils have been found in the patient's brain in large quantity. A previous study found that erythrosine B (ER), a red color food dye approved by FDA, inhibits the formation of amyloid beta fibril structures. Here, in an attempt to elucidate the inhibition mechanism, we performed molecular dynamics simulations to demonstrate the conformational change of $A{\beta}40$ induced by 2 ERs in atomistic detail. During the simulation, the ERs bound to the surfaces of both N-terminus and C-terminus regions of $A{\beta}40$ rapidly. The observed stacking of the ERs and the aromatic side chains near the N-terminus region suggests a possible inhibition mechanism in which disturbing the inter-chain stacking of PHEs destabilizes beta-sheet enriched in amyloid beta fibrils. The bound ERs block water molecules and thereby help stabilizing alpha helical structure at the main chain of C-terminus and interrupt the formation of the salt-bridge ASP23-LYS28 at the same time. Our findings can help better understanding of the current and upcoming treatment studies for Alzheimer's disease by suggesting inhibition mechanism of ER on the conformational transition of $A{\beta}40$ at the molecular level.

• The Journal of Korea Institute of Information, Electronics, and Communication Technology
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• v.14 no.5
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• pp.403-412
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• 2021

Alzheimer's disease (AD) is the most common cause of dementia, showing progressive neurodegeneration. Although oral medications for symptomatic improvement still take a huge part of treatment, there are several limitations caused by pharmacology-based real world clinic. In this respect, non-pharmacologic treatment for AD is rising to prominence. Transcranial direct current stimulation (tDCS) is a one of the non-invasive neuromodulation technique, using low-voltage direct current. In terms of safety, tDCS already has been proven through numerous previous reports. This review focused on behavioral, neurophysiologic and histopathologic improvement by applying tDCS in AD rodent models, thereby suggesting reliable background evidence for human-based tDCS study.

• Journal of the Korean Chemical Society
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• v.58 no.6
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• pp.553-559
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• 2014

Alzheimer's disease (AD) is a devastating neurodegenerative disease that represents the most common form of dementia among the elderly population. The deposition of aggregated ${\beta}$-amyloid ($A{\beta}$) senile plaques in the human brain is a classic observation in the neuropathology of AD, yet an understanding of the mechanism of their formation remains elusive. $A{\beta}$ is formed through endoproteolysis of the amyloid precursor protein (APP) by ${\beta}$-secretase (BACE1, ${\beta}$-site APP-cleaving enzyme) and ${\gamma}$-secretase. In this study, BACE1 protein was successfully over-expressed, purified, and refolded and utilized in a binding study with hispidin. We developed a simpler refolding method using a urea gradient and size-exclusion gel filtration to purify an active BACE1 protein variant, in larger quantities than that reported previously, and measured the binding affinity of hispidin to the BACE1 protein variant through isothermal titration calorimetry.

• 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.

• Journal of Yeungnam Medical Science
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• v.36 no.3
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• pp.183-191
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• 2019

Some patients with type 1 and type 2 diabetes mellitus (DM) present with cognitive dysfunctions. The pathophysiology underlying this complication is not well understood. Type 1 DM has been associated with a decrease in the speed of information processing, psychomotor efficiency, attention, mental flexibility, and visual perception. Longitudinal epidemiological studies of type 1 DM have indicated that chronic hyperglycemia and microvascular disease, rather than repeated severe hypoglycemia, are associated with the pathogenesis of DM-related cognitive dysfunction. However, severe hypoglycemic episodes may contribute to cognitive dysfunction in high-risk patients with DM. Type 2 DM has been associated with memory deficits, decreased psychomotor speed, and reduced frontal lobe/executive function. In type 2 DM, chronic hyperglycemia, long duration of DM, presence of vascular risk factors (e.g., hypertension and obesity), and microvascular and macrovascular complications are associated with the increased risk of developing cognitive dysfunction. The pathophysiology of cognitive dysfunction in individuals with DM include the following: (1) role of hyperglycemia, (2) role of vascular disease, (3) role of hypoglycemia, and (4) role of insulin resistance and amyloid. Recently, some investigators have proposed that type 3 DM is correlated to sporadic Alzheimer's disease. The molecular and biochemical consequences of insulin and insulin-like growth factor resistance in the brain compromise neuronal survival, energy production, gene expression, plasticity, and white matter integrity. If patients claim that their performance is worsening or if they ask about the effects of DM on functioning, screening and assessment are recommended.

• Journal of Integrative Natural Science
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• v.13 no.4
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• pp.170-180
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• 2020

Abnormal regulation, hyperphosphorylation, and aggregation of the tau protein are the hallmark of several types of dementia, including Alzheimer's Disease. Increased activity of Glycogen Synthase Kinase-3β (GSK-3β) in the Central Nervous System (CNS), increased the tau hyperphosphorylation and caused the neurofibrillary tangles (NFTs) formation in the brain cells. Over the last two decades, numerous adenosine triphosphate (ATP) competitive inhibitors have been discovered that show inhibitory activity against GSK-3β. But these compounds exhibited off-target effects which motivated researchers to find new GSK-3β inhibitors. In the present study, we have collected the dataset of 31 C-Glycosylflavones derivatives that showed inhibitory activity against GSK-3β. Among the dataset, the most active compound was docked with the GSK-3β and molecular dynamics (MD) simulation was performed for 50 ns. Based on the 50 ns MD pose of the most active compound, the other dataset compounds were sketched, minimized, and aligned. The 3D-QSAR based Comparative Molecular Field Analysis (CoMFA) model was developed, which showed a reasonable value of q2=0.664 and r2=0.920. The contour maps generated based on the CoMFA model elaborated on the favorable substitutions at the R2 position. This study could assist in the future development of new GSK-3β inhibitors.

• Journal of the Korean Society of Radiology
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• v.83 no.3
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• pp.527-537
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• 2022

Iron has a vital role in the human body, including the central nervous system. Increased deposition of iron in the brain has been reported in aging and important neurodegenerative diseases. Owing to the unique magnetic resonance properties of iron, MRI has great potential for in vivo assessment of iron deposition, distribution, and non-invasive quantification. In this paper, we will review the MRI methods for iron assessment and their changes in aging and neurodegenerative diseases, focusing on Alzheimer's disease. In addition, we will summarize the limitations of current approaches and introduce new areas and MRI methods for iron imaging that are expected in the future.

• Clinical Nutrition Research
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• v.11 no.3
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• pp.159-170
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• 2022

Ischemic stroke and Alzheimer's disease (AD) are representative geriatric diseases with a rapidly increasing prevalence worldwide. Recent studies have reported an association between ischemic stroke neuropathology and AD neuropathology. Ischemic stroke shares some similar characteristics with AD, such as glia activation-induced neuroinflammation, amyloid beta accumulation, and neuronal cell loss, as well as some common risk factors with AD progression. Although there are considerable similarities in neuropathology between ischemic stroke and AD, no studies have ever compared specific genetic changes of brain cortex between ischemic stroke and AD. Therefore, in this study, I compared the cerebral cortex transcriptome profile of 5xFAD mice, an AD mouse model, with those of middle cerebral artery occlusion (MCAO) mice, an ischemic stroke mouse model. The data showed that the expression of many genes with important functional implications in MCAO mouse brain cortex were related to synaptic dysfunction and neuronal cell death in 5xFAD mouse model. In addition, changes in various protein-coding RNAs involved in synaptic plasticity, amyloid beta accumulation, neurogenesis, neuronal differentiation, glial activation, inflammation and neurite outgrowth were observed. The findings could serve as an important basis for further studies to elucidate the pathophysiology of AD in patients with ischemic stroke.

• Journal of Oriental Neuropsychiatry
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• v.28 no.3
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• pp.263-274
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• 2017

Objectives: To identify the current status of Korean medical practice pattern, diagnosis and treatment of dementia through recognition survey, and to use it as a preliminary data for various dementia research. Methods: Questionnaires were developed through expert meetings. The disease was defined as dementia and mild cognitive impairment, and areas were designated to practice pattern, diagnosis and treatment. From December 18, 2016-January 18, 2017, 221 respondents, including 36 neuropsychiatrists of Korean Medicine and 185 general physicians (including other medical specialists) were included. Results: 1. In both groups, the most commonly used KCD (Korean standard classification of disease and cause of death) were in the order of Unspecified Alzheimer's Dementia (F00.9), Mild Cognitive Impairment (F06.7), and Unspecified Dementia (F03). 2. The most commonly used pattern identification were zang-fu and qi-blood-yin-yang in both groups. 3. Diagnostic evaluation tools were mainly conducted by MMSE, radiologic examination, K-DRS, GDS and CDR in both groups. 4. Both groups reported using acupuncture and herbal medicine mainly. 5. In both groups, the acupuncture method was used extensively in the order of Body, Scalp, and Sa-Am. 6. Neuropsychiatrists used a variety of herbal medicines such as Wonjiseokchangpo-san (Yuanzhushichangpu-san), Yukmijihwang-tang (Liuweidihuang-tang), Palmijihwang-won (Baweidihuang-won), Sunghyangjungki-san (Xingxiang Zhengqi-san) and Ondam-tanggami (Wendan-tangjiawei). General physicians used a variety of herbal medicines such as Ondam-tanggami (Wendan-tangjiawei), Bojungikgi-tang (Buzhongyiqi-tang), Yukmijihwang-tang (Liuweidihuang-tang). 7. Neuropsychiatrists used a variety of Korean herbal preparation products (benefit and non-benefit) such as Ekgan-sangajinpibanha (Yigan-sanjiachenpibanxia), Yukmijihwang-tang (Liuweidihuang-tang), Jodeung-san (houteng-san), Palmijihwang-won (Baweidihuang-won). General physicians used a variety of Korean herbal preparation products such as Bojungikgi-tang (Buzhongyiqi-tang), Banhabaegchulcheonma-tang (banxiabaizhutianma-tang), Yukmijihwang-tang (Liuweidihuang-tang), Ekgan-sangajinpibanha (Yigan-sanjiachenpibanxia), Palmijihwang-won (Baweidihuang-won). Conclusions: By confirming awareness of Korean medical doctors treating dementia in clinical fields and understanding differences between neuropsychiatrists of Korean medicine and general physicians, it can be used to understand guideline users' needs and confirm clinical questions during development of future clinical practice guidelines for dementia.

• Journal of Society of Preventive Korean Medicine
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• v.15 no.3
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• pp.39-49
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• 2011

Objectives : Vascular dementia is the second common cause of dementia after Alzheimer's disease. It assumed that the ratio of prescription drugs on vascular dementia are quite different from each hospital in Western medicine or Oriental medicine, respectively. The aim of this research is to collect and analyze the ratio of prescription drugs on vascular dementia in Western medicine or Oriental medicine in university hospitals. Methods : We collected and analyzed the data related to prescriptions on vascular dementia in the department of neurology in three university hospitals(A, B, C) and in the department of internal medicine in two Oriental medicine hospitals(Daegu Haany Oriental Hospital, Dong Eui Oriental Hospital). Results : In the department of neurology in A university hospital, donepezil(69.1%), memantine(14.0%), rivastigmine(12.3%), galantamine(4.5%) were prescribed in order. In B university hospital, galantamine(57.8%) donepezil(33.3%), rivastigmine(6.7%), donepezil with memantine(4.4%) were prescribed. In C university hospital, donepezil(62.0%), rivastigmine(25.0%), galantamine(7.0%) memantine(6.0%) were prescribed. The average frequencies of prescribed medication in the department of neurology in A, B, C university hospitals were donepezil(54.8%), galantamine(23.1%), rivastigmine(14.7%), memantine(7.4%). In Oriental medicine hospitals, various prescriptions have been used for vascular dementia. Among them, Ansincheongnoetang (安神淸腦湯) and Gamijihangeumja(加味地黃飮子) were often prescribed in Daegu Haany Oriental Hospital, and Bojungikgitang(補中益氣湯) in Dong Eui Oriental Hospital, too. Conclusions : Cholinesterase inhibitors such as donepezil, galantamine, rivastigmine and NMDA receptor inhibitor like memantine have been used as a drug of choice for vascular dementia in all surveyed university hospitals. In oriental hospitals, various prescriptions have been used for vascular dementia.