• Journal of Microbiology and Biotechnology
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• v.17 no.12
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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.

• Nutrition Research and Practice
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• v.14 no.6
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• pp.593-605
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• 2020

BACKGROUND/OBJECTIVES: Alzheimer's disease is common age-related neurodegenerative condition characterized by amyloid beta (Aβ) accumulation that leads cognitive impairment. In the present study, we investigated the protective effect of paeoniflorin (PF) against Aβ-induced neuroinflammation and the underlying mechanism in C6 glial cells. MATERIALS/METHODS: C6 glial cells were treated with PF and Aβ_25-35, and cell viability, nitric oxide (NO) production, and pro-inflammatory cytokine release were measured. Furthermore, the mechanism underlying the effect of PF on inflammatory responses and Aβ degradation was determined by Western blot. RESULTS: Aβ_25-35 significantly reduced cell viability, but this reduction was prevented by the pretreatment with PF. In addition, PF significantly inhibited Aβ_25-35-induced NO production in C6 glial cells. The secretion of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha was also significantly reduced by PF. Further mechanistic studies indicated that PF suppressed the production of these pro-inflammatory cytokines by regulating the nuclear factor-kappa B (NF-κB) pathway. The protein levels of inducible NO synthase and cyclooxygenase-2 were downregulated and phosphorylation of NF-κB was blocked by PF. However, PF elevated the protein expression of inhibitor kappa B-alpha and those of Aβ degrading enzymes, insulin degrading enzyme and neprilysin. CONCLUSIONS: These findings indicate that PF exerts protective effects against Aβ-mediated neuroinflammation by inhibiting NF-κB signaling, and these effects were associated with the enhanced activity of Aβ degradation enzymes.

• Korean Journal of Medicinal Crop Science
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• v.28 no.2
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• pp.85-94
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• 2020

Background: Alzheimer's disease (AD) is caused by various factors, such as cholinergic dysfunction, regulation of neurotrophic factor expression, and accumulation of amyloid-beta. We investigated whether or not a combination of Carthamus tinctorius L. seed and Taraxacum coreanum (CT) has a protective effect on scopolamine-induced memory impairment in a mouse model. Methods and Results: Mice were orally pretreated with CT (50, 100 and 200 mg/kg/day) for 14 days, and scopolamine (1 mg/kg/day) was injected intraperitoneally before subjecting them to behavior tests. CT-administered mice showed better novel object recognition and working memory ability than scopolamine-treated control mice. In T-maze and Morris water maze tests, CT (100 and 200 mg/kg/day) significantly increased space perceptive ability and occupancy to the target quadrant, respectively. In addition, 100 and 200 mg/kg/day of CT attenuated cholinergic dysfunction through inhibition of butyryl cholinesterase in brain tissue. Furthermore, CT-administered mice showed higher cyclic adenosine monophosphate-response element-binding protein (CREB) levels and lower amyloid precursor protein (APP) levels compared to scopolamine-treated control mice. Conclusions: CT improved scopolamine-induced memory impairment through inhibition of cholinergic dysfunction, up-regulation of CREB, and down-regulation of APP. Therefore, CT could be a useful therapeutic agent for AD with protective effects on cognitive impairment.

• 한국약용작물학회:학술대회논문집
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• 2008.11a
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• pp.312-313
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• 2008

• 한국약용작물학회:학술대회논문집
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• 2008.11a
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• pp.318-319
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• 2008

• 대한핵의학회:학술대회논문집
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• 2005.11a
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• pp.332.2-332.2
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• 2005

• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.350-357
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• 2018

Glial cells are receiving much attention since they have been recognized as important regulators of many aspects of brain function and disease. Recent evidence has revealed that two different glial cells, astrocytes and microglia, control synapse elimination under normal and pathological conditions via phagocytosis. Astrocytes use the MEGF10 and MERTK phagocytic pathways, and microglia use the classical complement pathway to recognize and eliminate unwanted synapses. Notably, glial phagocytosis also contributes to the clearance of disease-specific protein aggregates, such as ${\beta}$-amyloid, huntingtin, and ${\alpha}$-synuclein. Here we reivew recent findings showing that glial cells are active regulators in brain functions through phagocytosis and that changes in glial phagocytosis contribute to the pathogenesis of various neurodegenerative diseases. A better understanding of the cellular and molecular mechanisms of glial phagocytosis in healthy and diseased brains will greatly improve our current approach in treating these diseases.

• Ocean and Polar Research
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• v.39 no.1
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• pp.45-49
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• 2017

During the search for anticholinesterase compounds from marine organisms, we were able to isolate 6,6'-bieckol from a red alga, Grateloupia elliptica. This compound showed moderate acetylcholinesterase (AChE) inhibitory activity in a micromole range ($IC_{50}$ $44.5{\mu}M$). However, for butyrylcholinesterase (BuChE), a new target for the treatment of Alzheimer's disease (AD), it showed particularly potent inhibitory activity ($IC_{50}$ $27.4{\mu}M$), which is more potent compared to AChE. It also inhibits BACE-1, a new target for reducing the generation of ${\beta}-amyloid$.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.2
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• pp.374-380
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• 2009

Samryungbaikchul-san(SRBCS) has been used in oriental medicine for the treatments of gastrointestinal and neurological disorders. Here, potential protective function of SRBCS was investigated in neural tissues in Alzheimer's disease(AD) mouse model. In primary cultured cells from the spinal cord of newborn rats, treatment of ${\beta}$-amyloid peptide elevated cell counts positive to glial fibrillary acidic protein(GFAP) or caspase 3 immunoreactivity, but the co-treatment of SRBCS reduced positive cell counts. In vivo administration of scopolamine, an inhibitor of muscarinic receptor, resulted in increases in the number of glial fibrillary acidic protein(GFAP) and caspase 3-positive cells in hippocampal subfields, which was then decreased by the treatment of SRBCS or acetylcholinesterase inhibitor galathamine. The present data suggest that SRBCS may play a protective role in damaged neural tissues caused by scopolamine treatments in mice.

• Proceedings of the Korean Society of Plant Biotechnology Conference
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• 2002.04b
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• pp.188-188
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• 2002