• Laboraroty Animal Research
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• v.33 no.3
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• pp.244-250
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• 2017

${\alpha}$-Synuclein is abundantly expressed in neuronal tissue, plays an essential role in the pathogenesis of neurodegenerative disorders, and exerts a neuroprotective effect against oxidative stress. Cerebral ischemia causes severe neurological disorders and neuronal dysfunction. In this study, we examined ${\alpha}$-synuclein expression in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury and neuronal cells damaged by glutamate treatment. MCAO surgical operation was performed on male Sprague-Dawley rats, and brain samples were isolated 24 hours after MCAO. We confirmed neurological behavior deficit, infarction area, and histopathological changes following MCAO injury. A proteomic approach and Western blot analysis demonstrated a decrease in ${\alpha}$-synuclein in the cerebral cortices after MCAO injury. Moreover, glutamate treatment induced neuronal cell death and decreased ${\alpha}$-synuclein expression in a hippocampal-derived cell line in a dose-dependent manner. It is known that ${\alpha}$-synuclein regulates neuronal survival, and low levels of ${\alpha}$-synuclein expression result in cytotoxicity. Thus, these results suggest that cerebral ischemic injury leads to a reduction in ${\alpha}$-synuclein and consequently causes serious brain damage.

• Journal of Oriental Neuropsychiatry
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• v.31 no.2
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• pp.89-99
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• 2020

Objectives: The purpose of this study was to identify the needs of bio-signal devices for the diagnosis, assessment, and analysis of neurocognitive disorder in Korean medicine (KM) hospitals and clinics. Methods: A questionnaire was developed to survey the current status of medical device use, and diagnosis and interventions for patients with cognitive disorders in KM hospitals and clinics. November 11~December 2, 2019, 114 responses (71.9% completed) were collected by internet-based questionnaires from the members of the Korean society of Oriental Neuropsychiatry. Results: The clinical requests were in the descending order of hematology analyzer, ultrasound imaging system, and electroencephalography among the 15 most commonly used devices of which research would support for their clinical usability. The biosignal-based devices showed the highest research demands for patients with mild cognitive impairment rather than more severe stages of cognitive impairment. Prevention rather than diagnosis, or several treatment regimens was the strongest clinical area of the KM for patients with neurodegenerative cognitive impairment. Many responded that five to 10 minutes of test duration and 20,000 won to 30,000 won of cost would be appropriated for a new device to be developed. Conclusions: There were strong demands for the development of bio-signal devices for neurocognitive disorders among the KM doctors. Specifically, it showed high needs for the technology that can be used in the prevention area of cognitive disorders. Additionally, new medical devices to assess cognitive functions and to obtain KM pattern-related information were the high needs.

• BMB Reports
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• v.49 no.12
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• pp.671-680
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• 2016

Accumulating evidence indicates many brain functions are mediated by epigenetic regulation of neural genes, and their dysregulations result in neuronal disorders. Experiences such as learning and recall, as well as physical exercise, induce neuronal activation through epigenetic modifications and by changing the noncoding RNA profiles. Animal models, brain samples from patients, and the development of diverse analytical methods have broadened our understanding of epigenetic regulation in the brain. Diverse and specific epigenetic changes are suggested to correlate with neuronal development, learning and memory, aging and age-related neuronal diseases. Although the results show some discrepancies, a careful comparison of the data (including methods, regions and conditions examined) would clarify the problems confronted in understanding epigenetic regulation in the brain.

• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.238-245
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• 2007

Chronic formaldehyde inhalation studies have suggested its relativity to teratogenicity, cancer incidence, neurodegenerative and vascular disorders. Many toxicological data on the formaldehyde toxicity are available, but proteomic results showing complete protein profiles are limited. Therefore, alterations of protein expression patterns upon formaldehyde treatment were investigated in the human lung epithelial cell line. Differentially expressed proteins following formaldehyde treatment were analyzed on 2-dimensional gels, and further analyzed by MALDI-TOF to identify the proteins. Among the identified proteins, 24 proteins were notably up-regulated and 6 proteins were down-regulated. In particular, cytoskeleton related protein named vinculin and Rho GDP dissociation inhibitor which plays a key role in apoptosis increased remarkably.

• BMB Reports
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• v.50 no.8
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• pp.401-410
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• 2017

The protein disulfide isomerase (PDI) family is a group of multifunctional endoplasmic reticulum (ER) enzymes that mediate the formation of disulfide bonds, catalyze the cysteine-based redox reactions and assist the quality control of client proteins. Recent structural and functional studies have demonstrated that PDI members not only play an essential role in the proteostasis in the ER but also exert diverse effects in numerous human disorders including cancer and neurodegenerative diseases. Increasing evidence suggests that PDI is actively involved in the proliferation, survival, and metastasis of several types of cancer cells. Although the molecular mechanism by which PDI contributes to tumorigenesis and metastasis remains to be understood, PDI is now emerging as a new therapeutic target for cancer treatment. In fact, several attempts have been made to develop PDI inhibitors as anti-cancer drugs. In this review, we discuss the properties and diverse functions of human PDI proteins and focus on recent findings regarding their roles in the state of diseases including cancer and neurodegeneration.

• Molecules and Cells
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• v.43 no.10
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• pp.880-888
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• 2020

Inherited peripheral neuropathy is a heterogeneous group of peripheral neurodegenerative disorders including Charcot-Marie-Tooth disease. Many peripheral neuropathies often accompany impaired axonal construction and function. To study the molecular and cellular basis of axon-defective peripheral neuropathy, we explore the possibility of using Caenorhabditis elegans, a powerful nematode model equipped with a variety of genetics and imaging tools. In search of potential candidates of C. elegans peripheral neuropathy models, we monitored the movement and the body posture patterns of 26 C. elegans strains with disruption of genes associated with various peripheral neuropathies and compiled a database of their phenotypes. Our assay showed that movement features of the worms with mutations in HSPB1, MFN2, DYNC1H1, and KIF1B human homologues are significantly different from the control strain, suggesting they are viable candidates for C. elegans peripheral neuropathy models.

• BMB Reports
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• v.43 no.10
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• pp.683-687
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• 2010

Previous studies have shown that one of the primary causes of increased iron content in the brain may be the release of excess iron from intracellular iron storage molecules such as ferritin. Free iron generates ROS that cause oxidative cell damage. Carnosine and related compounds such as endogenous histidine dipetides have antioxidant activities. We have investigated the protective effects of carnosine and homocarnosine against oxidative damage of DNA induced by reaction of ferritin with $H_2O_2$. The results show that carnosine and homocarnosine prevented ferritin/$H_2O_2$-mediated DNA strand breakage. These compounds effectively inhibited ferritin/$H_2O_2$-mediated hydroxyl radical generation and decreased the mutagenicity of DNA induced by the ferritin/$H_2O_2$ reaction. Our results suggest that carnosine and related compounds might have antioxidant effects on DNA under pathophysiological conditions leading to degenerative damage such as neurodegenerative disorders.

• Biomolecules & Therapeutics
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• v.28 no.6
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• pp.503-511
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• 2020

Autophagy is a major catabolic process that maintains cell metabolism by degrading damaged organelles and other dysfunctional proteins via the lysosome. Abnormal regulation of this process has been known to be involved in the progression of pathophysiological diseases, such as cancer and neurodegenerative disorders. Although the mechanisms for the regulation of autophagic pathways are relatively well known, the precise regulation of this pathway in the treatment of cancer remains largely unknown. It is still complicated whether the regulation of autophagy is beneficial in improving cancer. Many studies have demonstrated that autophagy plays a dual role in cancer by suppressing the growth of tumors or the progression of cancer development, which seems to be dependent on unknown characteristics of various cancer types. This review summarizes the key targets involved in autophagy and malignant transformation. In addition, the opposing tumor-suppressive and oncogenic roles of autophagy in cancer, as well as potential clinical therapeutics utilizing either regulators of autophagy or combinatorial therapeutics with anti-cancer drugs have been discussed.

• Journal of Microbiology and Biotechnology
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• v.26 no.9
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• pp.1657-1660
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• 2016

Prion diseases are incurable neurodegenerative disorders. Our previous study demonstrated that polylysine was effective in prolonging the incubation period in a rodent model and in alleviating the scrapie prion protein (PrP^Sc) burden in the brain at the terminal stage of the disease. Here, we report that intraperitoneal administration of polylysine suppresses the accumulation of prions in the spleen during the early stages of the disease. This study supports the congruence of PrP^Sc inhibition by polylysine in both the spleen and brain.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.302.2-303
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• 2002

Oxidative stress has been implicated in the pathophysiology of many neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Baicalein. baicalin and wogonin. the major constituents of Scutellaria baicalensis. have been reported to exhibit antioxidant properties in many different bioassay systems. The present study evaluated neuroprotective effects of these flavonoids on various neuronal injuries induced in primary cultured rat cortical cells by oxidative stress. NMDA. oxygen-glucose deprivation. and $A{\beta}$(25-35). (omitted)