• Journal of Integrative Natural Science
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• v.4 no.3
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• pp.216-221
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• 2011

c-Jun N-terminal kinase-3 (JNK-3) has been shown to mediate neuronal apoptosis and make the promising therapeutic target for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and other CNS disorders. In order to better understand the structural and chemical features of JNK-3, comparative molecular field analysis (CoMFA) was performed on a series of 3,5-disubstituted quinolines derivatives. The best predictions were obtained CoMFA model ($q^2$=0.707, $r^2$=0.972) and the statistical parameters from the generated 3D-QSAR models were indicated that the data are well fitted and have high predictive ability. The resulting contour map from 3D-QSAR models might be helpful to design novel and more potent JNK3 derivatives.

• Bulletin of the Korean Chemical Society
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• v.32 no.9
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• pp.3421-3424
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• 2011

The endogenous neurotoxin, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), has been considered a potential causative factor for the pathogenesis of Parkinson's disease (PD). In this study, we examined oxidative modification of neurofilament-L (NF-L) induced by salsolinol. When disassembled NF-L was incubated with salsolinol, the aggregation of protein was increased with the concentration of sasolinol. The formation of carbonyl compound was obtained in salsolinol-mediated NF-L aggregates. This process was protected by free radical scavengers, such as N-acetyl-L-cysteine and glutathione. These results suggest that the aggregation of NF-L is mediated by salsolinol via the generation of free radicals. We also investigated the effects of copper ion on salsolinol-mediated NF-L modification. In the presence of copper ions, salsolinol enhanced the modification of NF-L. We suggest that salsolinol might be related to abnormal aggregation of NF-L which may be involved in the pathogenesis of neurodegenerative diseases and related disorders.

• IMMUNE NETWORK
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• v.12 no.2
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• pp.41-47
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• 2012

Contemporary studies illustrate that peripheral injuries activate glial components of the peripheral and central cellular circuitry. The subsequent release of glial stressors or activating signals contributes to neuropathic pain and neuroinflammation. Recent studies document the importance of glia in the development and persistence of neuropathic pain and neuroinflammation as a connecting link, thereby focusing attention on the glial pathology as the general underlying factor in essentially all age-related neurodegenerative diseases. There is wide agreement that excessive glial activation is a key process in nervous system disorders involving the release of strong pro-inflammatory cytokines, which can trigger worsening of multiple disease states. This review will briefly discuss the recent findings that have shed light on the molecular and cellular mechanisms of glia as a connecting link between neuropathic pain and neuroinflammation.

• Bulletin of the Korean Chemical Society
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• v.25 no.5
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• pp.625-628
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• 2004

Ceruloplasmin (CP), the blue oxidase present in all vertebrates, is the major copper-containing protein of plasma. It has been proposed that oxidation of L-3,4-dihydroxyphenylalanine (DOPA) may contribute to the pathogenesis of neurodegenerative disorders. The effect of the oxidized products of DOPA on the modification of human CP was investigated. When CP was incubated with the oxidized L-DOPA, the protein was induced to be aggregated and ferroxidase activity was decreased in a time-dependent manner. Radical scavengers and catalase significantly inhibited the oxidized DOPA-mediated CP aggregation. Copper chelatrors, Diethylenetriaminepenta acetic acid (DTPA) and Diethyldithiocarbamic acid (DDC), also inhibited the oxidative modification of CP. The results suggested that DOPA oxidation led to the formation of free radical and induced the CP aggregation.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.91-92
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• 2003

Oxidative stress induced by reactive oxygen intermediates (ROIs) has been implicated in a variety of human diseases including cancer, diabetes, rheumatoid arthritis and neurodegenerative disorders. Hydrogen peroxide ($H_2O$$_2$), a representative ROI which is produced during the cellular redox process, can cause cell death via apoptosis and/or necrosis depending on its concentrations. (omitted)

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.81-82
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• 2003

Recent studies suggest that inflammatory events are implicated in a variaty of human diseases such as cancer and neurodegenerative diseases, and non-steroidal anti-inflammatory drugs have beneficial effects for the treatment or prevention of these disorders. Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the prostaglandin(PG) synthesis, is induced by various pro-inflammatory stimuli including nitric oxide(NO) and has been reported to cause and/or aggravate neuronal cell death.(omitted)

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.10a
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• pp.125-132
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• 1995

In neurons, nitric oxide(NO) is produced by neuronal nitric oxide synthase following stimulation of N-methyl-D-aspartate(NMDA) receptors and the subsequent influx of Ca$\^$2+/. NO, induced in this manner, reportedly plays critical roles in neuronal plasticity, including neurite outgrowth, synaptic transmission, and long-term potentiation(LTP) (1-7). However, excessive activation of NMDA receptors has also been shown to be associated with various neurological disorders, including focal ischemia, epilepsy, trauma, neuropathic pain and chronic neurodegenerative maladies, such as Parkinson's disease, Hungtington's disease and amyotrophic lateral sclerosis(8). The paradox that nitric oxide(NO) has both neuroprotective and neurodestructive effects may be explained, at least in part, by the finding that NO effects on neurons are dependent on the redox state. This claim may be supported by the recent finding that tissue concentrations of cysteine approach 700 ${\mu}$M in settings of cerebral ischemia (9), levels of thiol that is expected to influence both the redox state of the system and the NO group itself(10).

• BMB Reports
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• v.46 no.2
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• pp.119-123
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• 2013

Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), an endogenous neurotoxin, is known to perform a role in the pathogenesis of Parkinson's disease (PD). In this study, we evaluated oxidative modification of cytochrome c occurring after incubation with salsolinol. When cytochrome c was incubated with salsolinol, protein aggregation increased in a dose-dependent manner. The formation of carbonyl compounds and the release of iron were obtained in salsolinol-treated cytochrome c. Salsolinol also led to the release of iron from cytochrome c. Reactive oxygen species (ROS) scavengers and iron specific chelator inhibited the salsolinol-mediated cytochrome c modification and carbonyl compound formation. It is suggested that oxidative damage of cytochrome c by salsolinol might induce the increase of iron content in cells, subsequently leading to the deleterious condition which was observed. This mechanism may, in part, provide an explanation for the deterioration of organs under neurodegenerative disorders such as PD.

• BMB Reports
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• v.41 no.9
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• pp.635-639
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• 2008

Acrolein is a highly reactive by product of lipid peroxidation and individuals with neurodegenerative disorders have been shown to contain elevated concentrations of this molecule in the brain. In the present study, we examined the pattern of neurofilament-L (NF-L) modification elicited by acrolein. When NF-L was incubated with acrolein, protein aggregation occurred in a acrolein concentration-dependent manner. Exposure of NF-L to acrolein also led to the generation of protein carbonyl compounds. Through the addition of free radical scavengers we observed a significant decrease in acrolein-mediated NF-L aggregation. These results indicate that free radicals may be involved in the modification of NF-L by acrolein. In addition, dityrosine crosslink formation was observed in acrolein-mediated NF-L aggregates and these aggregates displayed thioflavin T reactivity, reminiscent of amyloid. This study suggests that acrolein-mediated NF-L aggregation might be closely related to oxidative reactions, thus these reactions may play a critical role in neuro-degenerative diseases.

• Smart Media Journal
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• v.9 no.3
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• pp.9-17
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• 2020

Hippocampus is a complex brain structure embedded deep into the temporal lobe. Studies have shown that this structure gets affected by neurological and psychiatric disorders and it is a significant landmark for diagnosing neurodegenerative diseases. Hippocampus features play very significant roles in region-of-interest based analysis for disease diagnosis and prognosis. In this study, we have attempted to learn the embeddings of this important biomarker. As conventional metric learning methods for feature embedding is known to lacking in capturing semantic similarity among the data under study, we have trained deep Siamese convolutional neural network for learning metric of the hippocampus. We have exploited Gwangju Alzheimer's and Related Dementia cohort data set in our study. The input to the network was pairs of three-view patches (TVPs) of size 32 × 32 × 3. The positive samples were taken from the vicinity of a specified landmark for the hippocampus and negative samples were taken from random locations of the brain excluding hippocampi regions. We have achieved 98.72% accuracy in verifying hippocampus TVPs.