• 한국멀티미디어학회논문지
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• 제23권8호
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• pp.940-952
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• 2020

The Alzheimer's disease (AD) is a neurodegenerative disease commonly found in the elderly individuals. It is one of the most common forms of dementia; patients with AD suffer from a degradation of cognitive abilities over time. To correctly diagnose AD, compuated-aided system equipped with automatic classification algorithm is of great importance. In this paper, we propose a novel deep learning based classification algorithm that takes advantage of MRI biomarker images including brain areas of hippocampus and cerebrospinal fluid for the purpose of improving the AD classification performance. In particular, we develop a new approach that effectively applies MRI biomarker patch images as input to 3D Deep Convolution Neural Network. To integrate multiple classification results from multiple biomarker patch images, we proposed the effective confidence score fusion that combine classification scores generated from soft-max layer. Experimental results show that AD classification performance can be considerably enhanced by using our proposed approach. Compared to the conventional AD classification approach relying on entire MRI input, our proposed method can improve AD classification performance of up to 10.57% thanks to using biomarker patch images. Moreover, the proposed method can attain better or comparable AD classification performances, compared to state-of-the-art methods.

• BMB Reports
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• 제43권4호
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• pp.225-232
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• 2010

Parkinson's Disease (PD) is a common neurodegenerative disease characterized by the progressive degeneration of nigrostriatal dopaminergic (DA) neurons. Although the causative factors of PD remain elusive, many studies on PD animal models or humans suggest that glial activation along with neuroinflammatory processes contribute to the initiation or progression of PD. Additionally, several groups have proposed that dysfunction of the blood-brain barrier (BBB) combined with infiltration of peripheral immune cells play important roles in the degeneration of DA neurons. However, these neuroinflammatory events have only been investigated separately, and the issue of whether these phenomena are neuroprotective or neurotoxic remains controversial. We here review the current knowledge regarding the functions of these neuroinflammatory processes in the brain. Finally, we describe therapeutic strategies for the regulation of neuroinflammation with the goal of improving the symptoms of PD.

• Biomolecules & Therapeutics
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• 제22권4호
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• pp.275-281
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• 2014

Autophagy is a series of catabolic process mediating the bulk degradation of intracellular proteins and organelles through formation of a double-membrane vesicle, known as an autophagosome, and fusing with lysosome. Autophagy plays an important role of death-survival decisions in neuronal cells, which may influence to several neurodegenerative disorders including Parkinson's disease. Chebulagic acid, the major constituent of Terminalia chebula and Phyllanthus emblica, is a benzopyran tannin compound with various kinds of beneficial effects. This study was performed to investigate the autophagy enhancing effect of chebulagic acid on human neuroblastoma SH-SY5Y cell lines. We determined the effect of chebulagic acid on expression levels of autophagosome marker proteins such as, DOR/TP53INP2, Golgi-associated ATPase Enhancer of 16 kDa (GATE 16) and Light chain 3 II (LC3 II), as well as those of its upstream pathway proteins, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Beclin-1. All of those proteins were modulated by chebulagic acid treatment in a way of enhancing the autophagy. Additionally in our study, chebulagic acid also showed a protective effect against 1-methyl-4-phenylpyridinium ($MPP^+$) - induced cytotoxicity which mimics the pathological symptom of Parkinson's disease. This effect seems partially mediated by enhanced autophagy which increased the degradation of aggregated or misfolded proteins from cells. This study suggests that chebulagic acid is an attractive candidate as an autophagy-enhancing agent and therefore, it may provide a promising strategy to prevent or cure the diseases caused by accumulation of abnormal proteins including Parkinson's disease.

• Nutritional Sciences
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• 제9권2호
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• pp.61-67
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• 2006

Green tea has attracted attention with respect to its potential for preventing and treating neurodegenerative disease. The neurotoxin, 6-hydroxydopamine (6-OHDA), was used to produce experimental Parkinson's disease (PD) model. The purpose of this study was to investigate the effects of green tea diet on behavioral changes, striatal dopamine content, and hepatic antioxidant parameters of PD model rats. In this study, we used male Sprague-Dawley rats weighing $200\sim220g$ and injected 6-OHDA into the right substantia nigra and medial forebrain bundle of the brain. The supply of green tea diet was started at 2 weeks before 6-OHDA lesion and continually supplied during 0, 2, and 4 weeks after 6-OHDA lesion (GT-0, GT-2, GT-4). Behavioral disturbance was measured by the stepping and d-amphetamine drug-induced rotation tests. Then, we assayed the striatal dopamine content and the hepatic malondialdehyde (MDA), hydrogen peroxide $(H_2O_2)$, and superoxide dismutase (SOD) activity. The percentage of lesioned forepaw to non-lesioned forepaw step scores was the highest in GT-4 group among all groups at both 3 and 4 weeks after 6-OHDA lesion. At 4 weeks after 6-OHDA lesion, the rotation score was the lowest in GT-2 group (p<0.05). However, increasing rate of the rotation score from 2 to 4 weeks after 6-OHDA lesion was the lowest in GT-4 group. The striatal dopamine content was not significantly different among four groups by green tea diet. The hepatic MDA level was the lowest in GT-4 group among four groups. The hepatic SOD activity was increased with the prolongation of green tea diet period These results suggest that green tea diet affects behavioral changes in rats of PD model. It seems that continuous green tea supplementation has an influence on the reduction of behavioral disturbance and the hepatic MDA level. Accordingly, continuous green tea supplementation was recommended for the prevention and treatment of PD. However, further studies are needed to investigate the mechanisms and efficacy of green tea in PD.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.299-310
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• 2020

Alzheimer's disease (AD) is a multi-faceted neurodegenerative disease. Thus, current therapeutic strategies require multitarget-drug combinations to treat or prevent the disease. At the present time, single drugs have proven to be inadequate in terms of addressing the multifactorial pathology of AD, and multitarget-directed drug design has not been successful. Based on these points of views, it is judged that combinatorial drug therapies that target several pathogenic factors may offer more attractive therapeutic options. Thus, we explored that the combination therapy with lower doses of cilostazol and aripiprazole with add-on donepezil (CAD) might have potential in the pathogenesis of AD. In the present study, we found the superior efficacies of donepezil add-on with combinatorial mixture of cilostazol plus aripiprazole in modulation of expression of AD-relevant genes: Aβ accumulation, GSK-3β, P300, acetylated tau, phosphorylated-tau levels, and activation of α-secretase/ADAM 10 through SIRT1 activation in the N2a Swe cells expressing human APP Swedish mutation (N2a Swe cells). We also assessed that CAD synergistically raised acetylcholine release and choline acetyltransferase (CHAT) expression that were declined by increased β-amyloid level in the activated N2a Swe cells. Consequently, CAD treatment synergistically increased neurite elongation and improved cell viability through activations of PI3K, BDNF, β-catenin and α7-nicotinic cholinergic receptors in neuronal cells in the presence of Aβ_1-42. This work endorses the possibility for efficient treatment of AD by supporting the synergistic therapeutic potential of donepezil add-on therapy in combination with lower doses of cilostazol and aripiprazole.

• Natural Product Sciences
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• 제17권2호
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• pp.65-79
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• 2011

Reactive oxygen species potentially cause damage to cellular components including lipids, protein and DNA; this oxidative damage plays a key role in the pathogenesis of neurodegenerative disease, cardiovascular disease, metabolic disease and cancer. On the basis of the oxidative stress hypothesis, a number of studies have been performed to search for an efficient and safe antioxidant. Although in vitro studies have provided promising results, only a limited number of natural and synthetic antioxidants have been developed for clinical application due to their low efficacy and side-effects. Thus, the discovery of new antioxidants with marked efficacy and safety has attracted worldwide attention in recent decades. Since plants are recognized as important sources of natural antioxidants, our research has focused on the discovery of new naturally occurring antioxidants from medicinal plants. The purpose of this review is to open a new prospect in the field of search for natural antioxidants from medicinal plants by summarizing our recent findings. Using in vitro bioassay systems such as 2,2-diphenyl-1-picrylhydrazyl, superoxide radical scavenging tests and lipid peroxidation models, we have tested over than 350 species of medicinal plants for their antioxidant activity and selected several of them for further investigation. During the research on the discovery of effective natural antioxidants from the medicinal plants selected, we have isolated several new and known antioxidant compounds that include stilbene glycosides, phenolic glycosides, flavonoids, oligostilbenes, and coumarins. Our results suggest that the presence of antioxidant compounds in the medicinal plants might be associated with the traditional use to treat inflammation, cardiovascular disease and various chronic diseases.

• Journal of Acupuncture Research
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• 제23권2호
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• pp.33-46
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• 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 extracellular deposition of beta-amyloid peptide $(A{\beta})$ in cerebral plaques. $A{\beta}$ is derived from the ${\beta}-amyloid$ precursor protein (APP) by the enzymes, ${\beta}-$ and ${\eta}o-secretase$. Compounds that ${\beta}-$ or ${\eta}o-secretase$ inhibit activity, can reduce the production of $A{\beta}$ peptides, and thus have therapeutic potential in the treatment of AD. Increasing body of evidence has been demonstrated that Bee Venom(BV) Acupuncture 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 $NF-{\kappa}B$. In this study, I investigated possible effects of BV on memory dysfunction caused by lipopolysaccharide (LPS) and $A{\beta}$ through inhibition of secretases activities and $A{\beta}$ aggregation. I examined the improving effect of BV on the LPS (2.5 mg/Kg, i.p.)-induced memory dysfunction using passive avoidance response and water maze tests in the mice. BV (0.84, $1.67\;{\mu}g/ml$) reversed the LPS-induced memorial dysfunction in dose dependent manner. BV also dose-dependently attenuated LPS-induced ${\beta}$ and ${\eta}o-secretase$ activities in cerebral cortex and hippocampus of the mice brain. This study therefore suggests that BV acupuncture method may be useful for prevention of development or progression of AD.

• Interdisciplinary Bio Central
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• 제4권3호
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• pp.6.1-6.12
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• 2012

Parkinson's disease (PD) is a complicated neurodegenerative disorder although it is oftentimes defined by clinical motor symptoms originated from age dependent and progressive loss of dopaminergic neurons in the midbrain. The pathogenesis of PD involves dopaminergic and nondopaminergic neurons in many brain regions and the molecular mechanisms underlying the death of different cell types still remain to be elucidated. There are indications that PD causing disease processes occur in a global scale ranging from DNA to RNA, and proteins. Several PD-associated genes have been reported to play diverse roles in controlling cellular functions in different levels, such as chromatin structure, transcription, processing of mRNA, translational modulation, and posttranslational modification of proteins. The advent of quantitative high throughput screening (HTS) tools makes it possible to monitor systemic changes in DNA, RNA and proteins in PD models. Combined with dopamine neuron isolation or derivation of dopamine neurons from PD patient specific induced pluripotent stem cells (PD iPSCs), HTS techonologies will provide opportunities to draw PD causing sequences of molecular events in pathologically relevant PD samples. Here I discuss previous studies that identified molecular functions in which PD genes are involved, especially those signaling pathways that can be efficiently studied using HTS methodologies. Brief descriptions of quantitative and systemic tools looking at DNA, RNA and proteins will be followed. Finally, I will emphasize the use and potential benefits of PD iPSCs-derived dopaminergic neurons to screen signaling pathways that are initiated by PD linked gene mutations and thus causative for dopaminergic neurodegneration in PD.

• 대한약침학회지
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• 제10권2호통권23호
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• pp.25-30
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• 2007

Objectives : Free radical metabolism seems to occupy a remarkably common position in the mechanisms of aging and aging related disease. Oxidative damage to DNA, lipids. proteins and other molecules may contribute to the development of cancer, cardiovascular disease and possibly neurodegenerative disease. This study was designed to find out whether Carthami Flos Herbal-Acupuncture Solution can scavenge Nitric Oxide(NO) or not. SNAP is NO generator. NO concentration was estimated after 2,6, 12 and 24 hrs in no treatment group, after treatment with Vit. C or 1, 10, 100${\mu}$g/m1 of Carthami Flos Herbal-Acupuncture Solution. There was no significant scavenging effect of Carthami Flos Herbal-Acupuncture Solutionon NO after 2 hrs. But there was a significant scavenging effect of Cafhami Flos Herbal-Acupuncture Solution on NO in 10${\mu}$/m1 group after 6hrs. And there was a significant scavenging effect of carthami Flos Herbal-Acupuncture Solution on NO in 1, 10${\mu}$g/ml group after 12, 24 hrs. These results suggest that Carhami Flos Herbal-Acupuncture Solution has scavenging effect on NO. This study shows that Carthami Flos Herbal-Acupuncture Solution can be used for aging related disease and further studies are required to investigate the antioxidative effects of it.

• Journal of Veterinary Science
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• 제22권5호
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• pp.64.1-64.12
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• 2021

Background: Pituitary pars intermedia dysfunction (PPID), a neurodegenerative disease leading to reduced dopamine production, is a common disease in aged horses. The treatment is based on administration of the dopamine agonist pergolide. This drug has been related to valvular fibrosis in humans, but the cardiovascular effect of this drug has not yet been investigated in horses. Objectives: To determine whether pergolide induces valvular disease in horses or affects the cardiac function. Methods: Standard, tissue Doppler (TDE) and two-dimensional speckle tracking (STE) echocardiography were performed in horses with diagnosed PPID based on adrenocorticotropic hormone dosage. Measurements taken in horses treated with pergolide were compared with those from untreated horses with nonparametric t-tests. Furthermore, measurements from follow-up examinations performed at least three months after the initial exam were compared with a Wilcoxon signed rank test for repeated measurements in each group. Results: Twenty-three horses were included. None of the 12 horses under treatment developed valvular regurgitation. Furthermore, no differences in the measurements of the left ventricular systolic or diastolic function could be seen between the group of horses with treatment and those without treatment. Measurements taken in the follow-up exam did not differ compared to those taken in the initial exam in both groups. Conclusions: No changes of the left ventricular function assessed by TDE and STE could be shown in a small population of horses with confirmed PPID. Treatment with pergolide did not affect the ventricular function nor induce valvular disease.