• 통합자연과학논문집
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• 제5권1호
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• pp.6-12
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• 2012

c-Jun N-terminal kinase-3 (JNK-3) has been identified as a promising target for neuronal apoptosis and has the effective therapeutic for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and other CNS disorders. Herein, we report the essential structural and chemical parameters for JNK-3 inhibitors utilizing comparative molecular field similarity indices analysis (CoMSIA) using the derivatives of 3,5-disubstituted quinolines. The best predictions were obtained CoMSIA model (q2=0.834, r2=0.987) 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.

• 대한의생명과학회지
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• 제24권4호
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• pp.305-310
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• 2018

Microglia are emerging as critical regulators of innate immune responses in AD and other neurodegenerative disorders, highlighting the importance of understanding their molecular and cellular mechanisms. We attempted to determine the role of crosstalk signaling between $IFN-{\gamma}$ and $TGF-{\beta}$ in $A{\beta}$ clearance by microglia cells. We used in vitro and in vivo mouse models that recapitulated acute and chronic aspects of microglial responses to $A{\beta}$ peptides. We showed that crosstalk signaling between $TGF-{\beta}$ and Smad2 was an important mediator of neuro-inflammation. These findings suggest that microglial $TGF-{\beta}$ activity enhances the pathological progression to AD. As $TGF-{\beta}$ displays broad regulatory effects on beneficial microglial functions, the activation of inflammatory crosstalk signaling between $TGF-{\beta}$ and Smad2 may be a promising strategy to restore microglial functions, halt the progression of $A{\beta}$-driven pathology, and prevent AD development.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.153.1-153.1
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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. l5-Deoxy-$D^{12, 14}$ prostaglandin $J_2$ (15d-$PGJ_2$), a dehydration product of prostaglandin $D_2$, has been reportd to possess a number of biological activities such as anti-inflammatory, anticarcinogenic, and antioxidative properties. (omitted)

• International Journal of Oral Biology
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• 제46권2호
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• pp.74-80
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• 2021

Autophagy is an evolutionarily well-conserved cellular homeostasis program that responds to various cellular stresses and degrades unnecessary or harmful intracellular materials in lysosomes. Accumulating evidence has shown that autophagy dysfunction often results in various human pathophysiological conditions, including metabolic disorders, cancers, and neurodegenerative diseases. The discovery of an autophagy machinery protein network has revealed underlying molecular mechanisms of autophagy, and advances in the understanding of its regulatory mechanism have provided novel therapeutic targets for treating human diseases. Recently, reports have emerged on the involvement of autophagy in oral squamous cell carcinoma (OSCC). Although the role of autophagy in cancer therapy is controversial, the beneficial use of the induction of autophagic cell death in OSCC has drawn significant attention. In this review, the types of autophagy, mechanism of autophagosome biogenesis, and modulating molecules and therapeutic candidates affecting the induction of autophagic cell death in OSCC are briefly described.

• 대한치매학회지
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• 제22권1호
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• pp.16-27
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• 2023

Alzheimer's disease (AD), one of the most representative neurodegenerative diseases, has diverse neurobiological and pathophysiological mechanisms. Treatment strategies targeting a single mechanism have repeated faced failures because the mechanism of neuronal cell death is very complex that is not fully understood yet. Since complex mechanisms exist to explain AD, a variety of diagnostic biomarkers for diagnosing AD are required. Moreover, standardized evaluations for comprehensive diagnosis using neuropsychological, imaging, and laboratory tools are needed. In this review, we summarize the latest clinical, neuropsychological, imaging, and laboratory evaluations to diagnose patients with AD based on our own experience in conducting a prospective study.

• 대한한방내과학회지
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• 제41권3호
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• pp.326-338
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• 2020

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease that causes disorientation, mood swings, problems with language, and difficulty remembering recent events. Acetylcholinesterase inhibitors (AchEIs) and memantine have been used to slow the course of the disease, but they can neither modify its progression nor prevent disease onset. Previous studies have suggested that Kami-guibi-tang (KGT) could be beneficial for supporting cognitive function in AD patients, but few clinical trials have been published. This pilot study aimed to evaluate the effect of KGT in improving cognitive function in AD patients. Methods: The study will be a randomized, placebo-controlled, double-blind, single-center trial conducted using subjects diagnosed with mild AD by neurologists. Study subjects will be randomly assigned to either a treatment or control group. The treatment group will receive KGT granules for 24 weeks, while the control group will receive placebo granules. AchEI administration will be maintained in both groups during the entirety of the study. Subjects will be assessed using the following exams: the Seoul Neuropsychologic Screening Battery (SNSB) for cognitive function; brain magnetic resonance imaging (MRI) for brain metabolite, neurotransmitter, and cerebral blood flow (CBF) measurements; the Korean version of Quality of Life-Alzheimer's Disease (KQol-AD) for quality of life; the Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI) for neurobehavioral symptoms; blood tests for amyloid and tau proteins and general blood parameters; and electrocardiography (ECG) before and after taking the medication. Discussion: Our findings will provide insight into the feasibility of large-scale trials to consolidate evidence for the efficacy of KGT for dementia treatment. Registration ID in CRIS: KCT0002904 (Clinical Research Information Service of the Republic of Korea).

• Journal of Microbiology and Biotechnology
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• 제17권12호
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• pp.2027-2032
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• 2007

[ ${\alpha}$ ]-Synuclein is the major component of Lewy bodies and responsible for the amyloid deposits observed in Parkinson's disease. Ordered filamentous aggregate formation of the natively unfolded ${\alpha}$-synuclein was investigated in vitro with the periodic ultrasonication. The ultrasonication induced the fibrillation of ${\alpha}$-synuclein, as the random structure gradually converted into a ${\beta}$-sheet structure. The resulting fibrils obtained at the stationary phase appeared heterogeneous in their size distribution, with the average length and height of $0.28\;{\mu}m{\pm}0.21\;{\mu}m$ and $5.6\;nm{\pm}1.9\;nm$, respectively. After additional extensive ultrasonication in the absence of monomeric ${\alpha}$-synuclein, the equilibrium between the fibril formation and its breakdown shifted to the disintegration of the preexisting fibrils. The resulting fragments served as nucleation centers for the subsequent seed-dependent accelerated fibrillation under a quiescent incubation condition. This self-seeding amplification process depended on the seed formation and subsequent alterations in their properties by the ultrasonication to a state that accretes the monomeric soluble protein more effectively than their reassociation of the seeds back to the original fibrils. Since many neurodegenerative disorders have been considered to be propagated via the seed-dependent amyloidosis, this study would provide a novel aspect of the significance of the seed structure and its properties leading to the acce]erated amyloid formation.

• Natural Product Sciences
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• 제24권3호
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• pp.148-154
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• 2018

Chronic oxidative stress due to the accumulation of reactive oxygen species (ROS) in neuronal cells ultimately leads to neurodegenerative diseases. The use of natural therapies for the prevention of ROS-induced cell damage and for the treatment of neurodegenerative disorders has shown promising results. In this study, we evaluated the neuroprotective effects of the ethyl acetate (EtOAc) fraction of A. okamotoanum against the hydrogen peroxide ($H_2O_2$)-induced oxidative stress in C6 glial cells. Results show that cell viability was decreased in cells incubated with $H_2O_2$, whereas the addition of EtOAc fraction treatments in such cells significantly increased viability. The EtOAc fraction showed the highest inhibitory activity against ROS production and it also decreased the expressions of inflammatory proteins including cyclooxygenase-2, inducible nitric oxide synthase and interleukin-$1{\beta}$. Furthermore, the EtOAc fraction inhibited apoptosis by regulating the protein expressions cleaved caspase -9, -3, poly ADP ribose polymerase, Bax and Bcl-2. Therefore, these results show that the EtOAc fraction of A. Okamotoanum exhibits neuroprotective effects against $H_2O_2$ induced oxidative damage by regulating the inflammatory reaction and apoptotic pathway.

• 농업과학연구
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• 제45권3호
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• pp.509-519
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• 2018

This study was investigated the anti-oxidant property and neuro-protective effect of Cirsium japonicum var. maackii (CJM) against oxidative stress in hydrogen peroxide ($H_2O_2$)-induced C6 glial cells. We measured the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydroxyl radical (${\cdot}OH$), and superoxide ($O_2{^-}$) radical scavenging activities of an ethanol extract and four fractions [n-Butanol, ethyl acetate (EtOAc), $CHCl_3$, and n-Hexane] from CJM. The results of this study show that the extract and all fractions from CJM had a dose-dependent DPPH radical scavenging activity. In particular, the EtOAc fraction exhibited the strongest scavenging effect with 88.23% at a concentration of $500{\mu}g/mL$. In addition, the EtOAc fraction from CJM also effectively scavenged ${\cdot}OH$ radicals and $O_2{^-}$ radicals, compared to other extract and fractions. In C6 glial cells, $H_2O_2$ markedly decreased the cell viability as well as increased lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) production. However, the EtOAc fraction of CJM attenuated the cellular damage from the oxidative stress by elevating the cell viability and inhibiting the LDH release and ROS over-production compared with the $H_2O_2$-treated control group. Our findings indicate that the EtOAc fraction from CJM has antioxidant effect and neuro-protective effect against oxidative stress, suggesting that it can be used as a natural antioxidant and therapeutic agent for the prevention of neurodegenerative disorders.

• Toxicological Research
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• 제34권3호
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• pp.267-279
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• 2018

Neurolathyrism is a neurodegenerative disorder characterized by spastic paraplegia resulting from the excessive consumption of Lathyrus sativus (Grass pea). ${\beta}$-N-Oxalyl-L-${\alpha},{\beta}$-diaminopropionic acid (L-ODAP) is the primary neurotoxic component in this pea. The present study attempted to evaluate the proteome-wide alterations in chick brain 2 hr and 4 hr post L-ODAP treatment. Proteomic analysis of chick brain homogenates revealed several proteins involved in cytoskeletal structure, signaling, cellular metabolism, free radical scavenging, oxidative stress and neurodegenerative disorders were initially up-regulated at 2 hr and later recovered to normal levels by 4 hr. Since L-ODAP mediated neurotoxicity is mainly by excitotoxicity and oxidative stress related dysfunctions, this study further evaluated the role of L-ODAP in apoptosis in vitro using human neuroblastoma cell line, IMR-32. The in vitro studies carried out at $200{\mu}M$ L-ODAP for 4 hr indicate minimal intracellular ROS generation and alteration of mitochondrial membrane potential though not leading to apoptotic cell death. L-ODAP at low concentrations can be explored as a stimulator of various reactive oxygen species (ROS) mediated cell signaling pathways not detrimental to cells. Insights from our study may provide a platform to explore the beneficial side of L-ODAP at lower concentrations. This study is of significance especially in view of the Government of India lifting the ban on cultivation of low toxin Lathyrus varieties and consumption of this lentil.