• Applied Microscopy
• /
• 제42권4호
• /
• pp.179-185
• /
• 2012

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Neuropathological hallmarks of AD are amyloid plaques, dystrophic neurite, and alteration of subcellular organelles. However, the morpho-functional study of this degenerative process and ultimate neuronal death remains poorly elucidated. In this study, immunohistochemical and ultrastructural analyses were performed to clarify the abnormal morphological alterations caused by the progression of AD in APP/PSEN1 transgenic mice, express human amyloid precursor protein, as a model for AD. In transgenic AD mice brain, the accumulation of Amyloid ${\beta}$ plaques and well-developed dystrophic neurites containing anti-LC3 antibody-positive autophagosomes were detected in the hippocampus and cortex regions. We also found severe disruption of mitochondrial cristae using high-voltage electron microscopy and three-dimensional electron tomography (3D tomography). These results provide morpho-functional evidence on the alteration of subcellular organelles in AD and may help in the investigation of the pathogenesis of AD.

• 동의신경정신과학회지
• /
• 제12궈1호
• /
• pp.151-167
• /
• 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.

• International Journal of Oral Biology
• /
• 제45권2호
• /
• pp.33-41
• /
• 2020

Neuroinflammation is known as the main mechanism implicated in the advancement of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The main feature of neuroinflammation is associated with the activation of microglia. The activated microglia increase proinflammatory cytokine production and induce progressive neuronal cell death. Citrus flavonoids show neuroprotective effects that are associated with the anti-inflammatory action of flavonoids in neurodegenerative diseases. Among these citrus flavonoids, kaempferol, naringin, and nobiletin show inhibitory effects on nuclear factor-κB and mitogen-activated protein kinase signaling pathways that can modulate inflammatory conditions in microglial cells. In the present review, we present the anti-inflammatory activities of citrus flavonoids and therapeutic potential of flavonoids as neuroprotective agents.

• Journal of Ginseng Research
• /
• 제45권6호
• /
• pp.665-675
• /
• 2021

Background: Ginsenoside Rg1 (Rg1), an active ingredient in ginseng, may be a potential agent for the treatment of Alzheimer's disease (AD). However, the protective effect of Rg1 on neurodegeneration in AD and its mechanism of action are still incompletely understood. Methods: Wild type (WT) and APP/PS1 AD mice, from 6 to 9 months old, were used in the experiment. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral changes. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction (q-PCR) were used to examine postsynaptic density 95 (PSD95) expression, amyloid beta (Aβ) deposition, Tau and phosphorylated Tau (p-Tau) expression, reactive oxygen species (ROS) production, and NAPDH oxidase 2 (NOX2) expression. Results: Rg1 treatment for 12 weeks significantly ameliorated cognitive impairments and neuronal damage and decreased the p-Tau level, amyloid precursor protein (APP) expression, and Aβ generation in APP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the ROS level and NOX2 expression in the hippocampus and cortex of APP/PS1 mice. Conclusions: Rg1 alleviates cognitive impairments, neuronal damage, and reduce Aβ deposition by inhibiting NOX2 activation in APP/PS1 mice.

• 한국응용과학기술학회지
• /
• 제35권2호
• /
• pp.389-398
• /
• 2018

본 연구는 노루궁뎅이버섯 균사체로 발효시킨 엄나무 추출물의 항산화 및 항아밀로이드 활성을 알아보고자 하였다. 항산화 활성은 2,2-diphenyl-1-picrylhydrazyl(DPPH) radical, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) radical 소거 측정법을 사용하여 관찰하였다. 엄나무추출물(KP), 노루궁뎅이버섯 균사체 추출물(HE), 엄나무 발효물(KP-HE)에서 모두 라디칼 소거활성이 관찰되었다. 그러나 KP-HE가 KP와 HE에 비해서 더 높은 소거 활성을 갖는 것으로 관찰되었다. KP-HE는 peroxyl radical에 의한 DNA의 산화적 손상을 억제하였다. 알츠하이머병 (Alzheimer's disease: AD)과 관련 있는 $A{\beta}_{1-42}$의 응집에 KP, HE, KP-HE가 어떤 영향을 미치는 지를 알아보았다. KP와 HE는 $A{\beta}_{1-42}$의 응집에 거의 영향을 미치지 않았고 KP-HE는 $A{\beta}_{1-42}$의 응집을 효과적으로 억제하였다. 또한 $A{\beta}_{1-42}$에 의한 신경세포 사멸에 엄나무 발효물을 $300{\mu}g/mL$ 농도로 전 처리한 세포생존율은 20.3% 높게 증가되었다. 또한 엄나무 발효물을 $50{\mu}g/mL$ 농도로 처리했을 경우 세포 내 ROS의 축적이 유의적으로 감소되었다. 결론적으로 본 연구에서 관찰된 결과들을 통해 엄나무 발효물은 항산화 및 항아밀로이드 활성을 가지는 것으로 확인되었다. 따라서 엄나무 발효물은 알츠하이머병과 같은 퇴행성 뇌질환을 예방할 수 있는 식품소재로 이용될 수 있을 것으로 사료된다.

• Ocean and Polar Research
• /
• 제39권1호
• /
• pp.45-49
• /
• 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 ${\beta}-amyloid$.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
• /
• pp.193-194
• /
• 1998

Recently, evaluation of brain transport of taurine which is possible to effect on Alzheimer's disease has investigated in rats. Also, internal carotid artery perfusion (ICAP) method is very useful for measuring of blood-brain barrier (BBB) permeability in rats. But ICAP has difficulties to evaluate of BBB permeability in mice especially. In the present study examines neuropharmaceutials permeability through the BBB in mice by common carotid artery perfusion (CCAP) method that modify ICAP method and require simple surgery. The external carotid artery (ECA) is cannulated with coagulating pterygopalatine artery (PPA) on ICAP method, while CCA is cannulated without coagulating PPA on CCAP method. The CCAP method require 4-5 fold higher infusion rate than ICAP method because an additional factor of 2 must be incorporated to adjust for fluid loss to the extracerebral circulation.

• 동의생리병리학회지
• /
• 제21권1호
• /
• pp.190-198
• /
• 2007

Alzheimer's disease, a representative neurodegenerative disorder, is characterized by the presence of senile plaques and neurofibrillary tangles accompanied by neuronal damages. b-Amyloid peptide is considered to be responsible for the formation of senile plagues that accumulate in the brains of patients with Alzheimer's disease. There has been compelling evidence supporting that b-amyloid-induced cytotoxicity is mediated through generation of reactive oxygen species. In this study, we have investigated the possible protective effect of Rehmannia glutihosaagainst b-amyloid-induced oxidative ceil death in cultured human neuroblastoma SH-SY5Y cells. SH-SY5Y cells treated with b-amyloid underwent apoptotic death as determined by morphological features and positive in situterminal end-labeling (TUNEL staining). Rehmannia glutinosawater extract, wine, and vinegar pretreatments attenuated b-amyloid-induced cytotoxicity and apoptosis. Rehmannia glutinosa vinegar exhibited maximum protective effect by increasing the expression of anti-apoptotic protein, Bcl-2. in addition to oxidative stress, b-amyloid-treatment caused nitrosative stress via marked increase in the levels of nitric oxide, which was effectively blocked by Rehmannia glutinosa. To further explore the possible molecular mechanisms underlying the protective effect of Rehmannia glutinosa, we assessed the mRNA expression of cellular antioxidant enzymes. Treatment of Rehmannia glutinosa vinegar led to up-regulation of heme oxygemase-1 and catalase. These results suggest that Rehmannia glutinosa could modulate oxidative neuronal cell death caused by b-amyloid and may have preventive or therapeutic potential in the management of Alzheimer's disease. Particularly, Rehmannia glutinosa vinegar can augment cellular antioxidant capacity, there by exhibiting higher neuroprotective potential.

• Journal of Acupuncture Research
• /
• 제23권3호
• /
• pp.103-115
• /
• 2006

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disease associated with aging in the human population. This disease is characterized by the following 4 structural changes : Atrophy of the Cortex, Parasympathetic, and other neural cells, the existence of Neurofibrillary tangles (NFTs), and the accumulation of Senile plaques. NFTs and Senile plaques is known to be the index of this disease. Senile plaques disturbs the neutro transmission and depletes of Acetylcholine. So, Recovery of Acetylcholine is the primal objective for treating Alzheimer's disease. So, Inhibiting the activity of Acetylcholine Esterase (AChE), which causes the hydrolysus of acetylcholine into choline and acetate, can be seen as a key role for treating Alzheimer's disease. Increasing body of evidence has been demonstrated that Bee Venom Acupuncture (BV) could compete with complex protein involving in multiple step of $NF-_{\kappa}B$ activation and exert the anti -inflammatory potential of combined inhibition of the prostanoid and nitric oxide synthesis systems by inhibition of IKK and $NF-_{\kappa}B$. The effect of BV through behavioral tests after memory impairment induced by Scopolamine. We examined the improving effect of BV on the Scopolamine (1 mg/Kg, i.p.)-induced memorial impairment using passive avoidance response and water maze tests in the mice. BV (0.84, $1.67\;{\mu}g/ml$) reversed the Scopolamine-induced memorial impairment in dose dependent manner. This study therefore suggests that BV acupuncture method may be useful for prevention of development or progression of AD.

• 대한한의학방제학회지
• /
• 제25권4호
• /
• pp.471-481
• /
• 2017

Objectives : Noemyeong-san (NMS) is a novel herbal prescription composed of five oriental medicinal herbs including Prunellae Spica, Betulae Cortex, Foeniculi Fructus, Asiasari Radix, and Clematidis Radix for treating Alzheimer's disease. In the present study, we investigated the effects and molecular mechanisms of NMS on BV2 microglia to evaluate the potential action of this formula for preventing or treating neurodegenerative disease such as Alzheimer's disease. Methods : To determine the cytotoxicity of NMS on BV2 microglia, the MTT assay was performed. The effects of NMS on lipopolysaccharide (LPS)-stimulated BV2 microglia were determined with a nitric oxide (NO) assay and western blots for inflammatory mediator-related proteins, mitogen activated protein kinases (MAPKs), nuclear factor kappa B (NF-${\kappa}B$) pathway-related proteins, and heme oxygenase-1 (HO-1). Result : NMS inhibited induction of iNOS and COX-2 as well as NO production without affecting the cell viability in LPS-stimulated BV2 microglia. NMS also suppressed activation of ERK and p38 MAPK among main kinases of MAPKs as well as NF-${\kappa}B$ by LPS stimulation. Furthermore, NMS dose-dependently induced the expression of HO-1 and the inhibitory effect of NMS on the production of NO were blocked by pretreatment with an HO-1 inhibitor, Snpp. Conclusions : These results demonstrate that NMS has potent anti-neuroinflammatory effect on the LPS-stimulated microglia. These findings provide evidences for NMS to be considered as a new prescription for preventing or treating neurodegenerative disease such as Alzheimer's disease.