• Biomedical Science Letters
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• v.27 no.3
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• pp.182-186
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• 2021

Parkinson disease (PD) is becoming one of the most neurodegenerative disorder worldwide. The deposited aggregates have been connected in the pathophysiology of PD, which are degraded either by ubiquitin-proteasomal system (UPS) or autophagy-lysosomal pathway (ALP). Leucin-rich repeat kinase 2 (LRRK2), one of the neurodegenerative proteins of PD is also stringently controlled by both UPS and ALP degradation as well. However, the polyubiquitination pattern of LRRK2 aggregates is largely unknown. Here, we found that K63-linked polyubiquitinations of G2019S mutant, most familial variant for PD, is highly enhanced compared to those of wild type LRRK2 (WT). In addition, in the presence of overexpressed p62/SQSTM-1, ubiquitination of LRRK2 WT or D1994A was reduced, whereas G2019S mutant was not diminished significantly. Therefore, we propose that degradation of G2019S via UPS is more involved with K63-linked ubiquitination than K48-linked ubiquitination, and overexpressed p62/SQSTM-1 does not enhance degradative effect on G2019S variant.

• Mass Spectrometry Letters
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• v.14 no.3
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• pp.57-78
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• 2023

Understanding the chemical composition of the brain helps researchers comprehend various neurological processes effectively. Understanding of the fundamental pathological processes that underpin many neurodegenerative disorders has recently advanced thanks to the advent of innovative bioanalytical techniques that allow high sensitivity and specificity with chemical imaging at high resolution in tissues and cells. Mass spectrometry imaging [MSI] has become more common in biomedical research to map the spatial distribution of biomolecules in situ. The technique enables complete and untargeted delineation of the in-situ distribution characteristics of proteins, metabolites, lipids, and peptides. MSI's superior molecular specificity gives it a significant edge over traditional histochemical methods. Recent years have seen a significant increase in MSI, which is capable of simultaneously mapping the distribution of thousands of biomolecules in the tissue specimen at a high resolution and is otherwise beyond the scope of other molecular imaging techniques. This review aims to acquaint the reader with the MSI experimental workflow, significant recent advancements, and implementations of MSI techniques in visualizing the anatomical distribution of neurochemicals in the human brain in relation to various neurogenerative diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.544-552
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• 2004

In oriental medicine, Radix Polygalae(RP) has been to treat tremors et al. But the mechanism how to decrease tremors was not known. The purpose of this study was to investigate the effect of RP on neurodegenerative disease. We used RP to execute the study of this defense mechanism on dopamine-induced cell death in human SH-SY5Y dopaminergic neuroblastoma cells. MTT assay was used to know the cytotoxicity of dopamine and the defense mechanism. As a result of this experiment, dopamine had cytotoxicity in human SH-SY5Y cells, but when it treated with RP, the cell survival rate increased. This suppressed the cell apoptosis, activation of caspase-3 protease, production of ROS, and repair of membrane potential change. In conclusion, RP has the protective effect on dopamine-induced cell death in human SH-SY5Y dopaminergic neuroblastoma cells, so this could be an effective agent on the neurodegenerative disease like Parkinsonism.

• Food Science and Biotechnology
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• v.15 no.2
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• pp.244-247
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• 2006

Neuronal cell death significantly contributes to neuronal loss in neurological injury and disease. Typically, neuronal loss or destruction upon exposure to neurotoxins, oxidative stress, or DNA damage causes neurodegenerative diseases such as Alzheimer's disease. In this study, we attempted to determine whether ginsenoside Rg3 from red ginseng has a neuroprotective effect via an anti-apoptotic role induced by S-nitroso-N-acetylpenicillamine (SNAP) at the molecular level. We also investigated the antioxidant effect of Rg3 using a metal-catalyzed reaction with $Cu^{2+}/H_2O_2$. Our results showed that Rg3 ($40-100\;{\mu}g/mL$) protected SK-N-MC neuroblastoma cells under cytotoxic conditions and effectively protected DNA from fragmentation. In the signal pathway, caspase-3, and poly (ADP-ribose) polymerase (PARP) were kept at an inactivated status when pretreated with Rg3 in all ranges. In particular, the important upstream p-Akt signal pathway was increased in a dose-dependent manner, which indicates that Rg3 may contribute to cell survival. We also found that oxidative stress can be mitigated by Rg3. Therefore, we have concluded that Rg3 plays a certain role in neurodegenerative pathogenesis via an anti apoptotic, antioxidative effect.

• Toxicological Research
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• v.30 no.4
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• pp.243-250
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• 2014

Mitochondrial integrity is critical for maintaining proper cellular functions. A key aspect of regulating mitochondrial homeostasis is removing damaged mitochondria through autophagy, a process called mitophagy. Autophagy dysfunction in various disease states can inactivate mitophagy and cause cell death, and defects in mitophagy are becoming increasingly recognized in a wide range of diseases from liver injuries to neurodegenerative diseases. Here we highlight our current knowledge on the mechanisms of mitophagy, and discuss how alterations in mitophagy contribute to disease pathogenesis. We also discuss mitochondrial dynamics and potential interactions between mitochondrial fusion, fission and mitophagy.

• Molecular & Cellular Toxicology
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• v.1 no.1
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• pp.40-45
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• 2005

Ursodeoxycholic acid (UDCA) has long been used as an adjuvant or first choice of therapy for liver disease. Commonly, UDCA has been reported to play a role in improving hyperbilirubinemia and disorder of bromsulphalein. More commonly, UDCA has been used in reducing the rate of cholesterol level in bile juice that can cause cholesterol stone. The effects on the promotion of bile acid release that leads an excretion of toxic materials and wastes produced in liver cells as well as various arrays of liver disease such as hepatitis. Other than already reported in clinical use, immunosuppressive effect has been studied, especially in transplantation. In the study, we hypothesized that UDCA might have a certain role in anti-inflammation through a preventive effect of pro-inflammatory potentials in the brain macrophages, microglia. We found that the treatment of $200\;{\mu}g/ml$ UDCA effectively suppressed the pro-inflammatory mediators (i.e. nitric oxide and interleukin-$1{\beta}$) in rat microglia compared to comparators. Interestingly, RT-PCR analysis suggested that UDCA strongly attenuated the expression of $IL-1{\beta}$ that was comparable with cyclosporine A at 48 h incubation. Conclusively, we found that UDCA may playa cytoprotective role in microglial cells through direct or indirect pathways by scavenging a toxic compound or an anti-inflammatory effect, which are known as major causes of neurodegenerative diseases.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2002.09a
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• pp.341-344
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• 2002

Neurodegenerative disorders, like Alzheimer's disease, are often accompanied by reduced brain perfusion (cerebral blood flow). Using the intrinsic magnetic properties of water, arterial spin labeling magnetic resonance imaging (ASLMRI) can map brain perfusion without injection of radioactive tracers or contrast agents. However, accuracy in measuring perfusion with ASL-MRI can be limited because of contributions to the signal from stationary spins and because of signal modulations due to transient magnetic field effects. The goal was to optimize ASL-MRI for perfusion measurements in the aging human brain, including brains with Alzheimer's disease. A new ASL-MRI sequence was designed and evaluated on phantom and humans. Image texture analysis was performed to test quantitatively improvements. Compared to other ASL-MRI methods, the newly designed sequence provided improved signal to noise ratio improved signal uniformity across slices, and thus, increased measurement reliability. This new ASL-MRI sequence should therefore provide improved measurements of regional changes of brain perfusion in normal aging and neurodegenerative disorders.

• Journal of Mushroom
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• v.12 no.2
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• pp.77-81
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• 2014

Mushrooms are considered not only as food but also for source of physiologically beneficial medicines. The culinary-medicinal mushrooms may important role in the prevention of age-associated neurological dysfunctions, including Alzheimer's and Parkinson's diseases. Hericium erinaceus (H. erinaceus), is edible mushrooms, is a parasitic fungus that grows hanging off of logs and trees and well established candidate for brain and nerve health. H. erinaceus contains high amounts of antioxidants, beta-glucan, polysaccharides and a potent catalyst for brain tissue regeneration and helps to improve memory and cognitive functions. Its fruiting bodies and the fungal mycelia exhibit various pharmacological activities, including the enhancement of the immune system, antitumor, hypoglycemic and anti-aging properties. H. erinaceus stimulates the synthesis of Nerve Growth Factor (NGF) which is the primary protein nutrient responsible for enhancing and repairing neurological disorders. Especially hericenones and erinacines isolated from its fruitin body stimulate NGF, synthesis. This fungus is also utilized to regulate blood levels of glucose, triglycerides and cholesterol. H. erinaceus can be considered as useful therapeutic agents in the management and/or treatment of neurodegeneration diseases. However, this review focuses on in vitro, in vivo and clinical trials for neurodegerative disease.

• Journal of Ginseng Research
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• v.31 no.3
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• pp.127-136
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• 2007

Ginseng, the root of Panax species, is a well-known herbal medicine. It has been used as traditional medicine in Korea, China and Japan for thousands of years and now is a popular and worldwide natural medicine. The active principles of ginseng are ginsenosides which are also called ginseng saponins. Traditionally ginseng has been used primarily as a tonic to invigorate weak body functions and help the restoration of homeostasis. Current in vivo and in vitro studies demonstrate its beneficial effects in a wide range of pathological conditions such as cardiovascular diseases, cancer, immune deficiency and hepatotoxicity. Moreover, recent research indicates that some of ginseng's active ingredients exert beneficial actions on aging and neurodegenerative disorders such as Parkinson´s disease. Essentially, antioxidant, antiinflammatory, anti-apoptotic and immunostimulant activities are mostly underlying the postulated ginseng-mediated protective mechanisms. Next to animal studies, data from neural cell cultures contribute to the understanding of these mechanisms which involve decreasing nitric oxide, scavenging of free radicals and counteracting excitotoxicity. This paper focuses on own and other neuroprotective data on ginseng for dopaminergic neurons and intends to show aspects where neuroprotection e.g. by ginsenosides, additionally or preceding standard Parkinson therapy, could come about as a valuable contribution to slow neurodegenerative processes.

• Journal of Environmental Science International
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• v.31 no.5
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• pp.423-429
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• 2022

Parkinson's Disease (PD) is a chronic neurodegenerative disorder caused by the progressive loss of dopaminergic neurons, leading to decreased dopamine levels in the midbrain. Although the specific etiology of PD is not yet known, oxidative stress, inflammation, and subsequent apoptosis have been proposed to be closely related to PD pathophysiology. Cera Flava (CF) is a natural extract obtained from beehives and is isolated through the heating, compression, filtration, and purification of beehives. CF has been used in traditional medicines for its various clinical and pharmacological effects. However, its effects on neurodegenerative diseases are unknown. Therefore, we investigated the effects of CF against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in mice and explored the underlying mechanism of action. In MPTP-induced PC12 cells, CF protected NADH dehydrogenase activity and inhibited lactate dehydrogenase. In the mouse model, CF promoted recovery from movement impairments, prevented dopamine depletion, and protected against MPTP-induced dopaminergic neuronal degradation. Moreover, CF downregulated glial and microglial activation. Taken together, our results suggest that CF improves behavioral impairments and protects against dopamine depletion in MPTP-induced toxicity by inhibiting glial and microglial activation.