• 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.

• Biomolecules & Therapeutics
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• v.18 no.3
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• pp.235-245
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• 2010

Mitochondria have long been recognized as ATP engines for the cell and recently as a dynamic and mobile organelles that control cell death and life. This exquisite organelle is the site of reactive oxygen species production and is highly vulnerable to exogenous stresses, resulting in catastrophic damage to the cell. Mitochondrial dysfunction is linked to a wide range of age-associated degenerative diseases, such as metabolic syndrome, cardiovascular disease, and neurodegenerative diseases. Understanding the molecular mechanisms of mitochondria-dependent pathogenesis may provide important strategies to treat these diseases. Indeed, mitochondria are emerging therapeutic targets for the mitochondria-related diseases. In this paper, we review the recent concepts of mitochondrial biology and how mitochondria are involved in age-associated degenerative diseases. Furthermore, we summarize the therapeutics which target to improve mitochondrial functions.

• BMB Reports
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• v.43 no.10
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• pp.656-663
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• 2010

Amyloid precursor protein (APP), which is critically involved in the pathogenesis of Alzheimer's disease (AD), is cleaved by gamma/epsilon-secretase activity and results in the generation of different lengths of the APP Intracellular C-terminal Domain (AICD). In spite of its small size and short half-life, AICD has become the focus of studies on AD pathogenesis. Recently, it was demonstrated that AICD binds to different intracellular binding partners ('adaptor protein'), which regulate its stability and cellular localization. In terms of choice of adaptor protein, phosphorylation seems to play an important role. AICD and its various adaptor proteins are thought to take part in various cellular events, including regulation of gene transcription, apoptosis, calcium signaling, growth factor, and $NF-{\kappa}B$ pathway activation, as well as the production, trafficking, and processing of APP, and the modulation of cytoskeletal dynamics. This review discusses the possible roles of AICD in the pathogenesis of neurodegenerative diseases including AD.

• 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.

• KSBB Journal
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• v.28 no.5
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• pp.269-274
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• 2013

Motor neuron disease (MND) is a fatal neurodegenerative disorder caused by progressive and selective degeneration of motor neurons (MNs). Because of the versatile nature, stem cells have the potential to repair or replace the degenerated cells. In this review, we discussed stem cell based therapies including the use of embryonic stem cells (ESCs), neural stem cells (NSCs), induced pluripotent stem cells (iPSCs) and genetically engineered cells to produce the neurotrophic factors for the treatment of MND. To achieve this goal, the knowledge of specificity of the cell target, homing and special markers are required.

• 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.50 no.6
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• pp.299-307
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• 2017

Mitophagy is a process of selective removal of damaged or unnecessary mitochondria using autophagic machinery. Mitophagy plays an essential role in maintaining mitochondrial quality control and homeostasis. Mitochondrial dysfunctions and defective mitophagy in neurodegenerative diseases, cancer, and metabolic diseases indicate a close link between human disease and mitophagy. Furthermore, recent studies showing the involvement of mitophagy in differentiation and development, suggest that mitophagy may play a more active role in controlling cellular functions. A better understanding of mitophagy will provide insights about human disease and offer novel chance for treatment. This review mainly focuses on the recent implications for mitophagy in human diseases and normal physiology.

• CELLMED
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• v.2 no.1
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• pp.2.1-2.11
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• 2012

Tea polyphenols especially catechins have long been studied for their antioxidant and radical scavenging properties. Scientists throughout the world have investigated the usefulness of the regular green tea consumption in several disease conditions. In-vitro and in-vivo experiments on catechins especially epigallocatechingallate have revealed a significant role in many ways. Reactive oxygen species have been increasingly implicated in the pathogenesis of many diseases and important biological processes. Toxic effects of these oxidants, commonly referred to as oxidative stress, can cause cellular damage by oxidizing nucleic acids, proteins, and membrane lipids. Oxidative stress has been related to aging and age related disorders. It is found that in a wide variety of pathological processes, including cancer, atherosclerosis, neurological degeneration, Alzheimer's disease, ageing and autoimmune disorders, oxidative stress has its implications. Catechins have been reported to be useful in combating aging and age related disorders like cancer, cardiovascular disorders and neurodegenerative diseases. In this mini review we will discuss such studies done across the globe.

• YAKHAK HOEJI
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• v.55 no.6
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• pp.473-477
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• 2011

Alzheimer's disease (AD), one of the most common forms of dementia, is a progressive neurodegenerative disorder symptomatically characterized by the decline in memory and cognitive abilities. To date, the successful therapeutic strategy to treat AD is to maintain the levels of acetylcholine (ACh) by inhibiting acetylcholinesterase (AChE) to lead five drugs in clinical use. In this study, several coumarin derivatives were designed based on the lead structure of scopoletin and evaluated for their AChE inhibitory activities.