• 동의신경정신과학회지
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• 제16권1호
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• pp.81-96
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• 2005

This experiment was designed to investigate the effect of Dichroa febrifuga(DIF) on the Alzheimer’s disease. The effects of DIF extract on $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA of THP-1 cell treated by $A{\beta}$ plus LPS and amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ and AChE activity of PC-12 cell lysate treated by $A{\beta}$ plus $rIL-1{\beta}$ and behavior of memory deficit mice induced by scopolamine and mice glucose, uric acid, AChE activity of memory deficit rats induced by scopolamine were investigated, respectively. The results were summarized as follows ; 1. DIF extract suppressed APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$. 2. DIF extract suppressed $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA in THP-1 cell treated by LPS. 3. DIF extract suppressed AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$. 4. DIF extract increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit rats induced by scopolamine. 5. DIF extract group showed significantly inhibitory effect on the memory deficit of mice induced by scopolamine in the experiment of Morris water maze. According to the above results, it is suggested that DIF extract might be usefully applied for prevention and treatment of Alzheimer’s disease and memory deficit.

• 동의신경정신과학회지
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• 제15권2호
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• pp.119-139
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• 2004

This research investigates the effect of the Hibiscus syriacus(HSS) on Alzheimer's disease. Specifically, the effects of the HSS extract on (1) $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ mRNA of PC-12 cells treated with LPS; (2) amyloid precursor proteins(APP), acetylcholinesterase(AChE), and glial fibrillary acidic protein(GFAP) mRNA of PC-12 cells treated with CT-105; (3) the AChE activity and the APP production of PC-12 cell treated with CT-105; (4) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, $IL-1{\beta}$ mRNA, $TNF-{\alpha}$ mRNA, and reactive oxygen species(ROS); (5) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. The results were summarized below ; 1. The HSS extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in THP-l cells treated with LPS. 2. The HSS extract suppressed the expression of APP, AChE, and GFAP mRNA in PC-12 cells treated with CT-105. 3. The HSS extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 4. For the HSS extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 5. The HSS extract suppressed the over-expression of $IL-1{\beta}$, $TNF-{\alpha}$, $IL-1{\beta}$ and $TNF-{\alpha}$ mRNA, CD68/GFAP, ROS in the mice with Alzheimer's disease induced by ${\beta}A$. 6. The HSS extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. These results suggest that the HSS extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the HSS extract for Alzheimer's disease is suggested for future research.

• 약학회지
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• 제51권4호
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• pp.264-269
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• 2007

Alzheimer’s disease (AD) is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}-amyloid $ (A ${\beta}$) peptides, which are generated by processing of amyloid precursor protein (APP). It is urgent to develop effective therapies for the treatment of AD, since our society rapidly accelerate aging. A${\beta}$ peptides have been believed to be neurotoxic and now are also considered to have effects on the mechanism of memory formation. In this study, effects of radicicol on the metabolism of APP were analyzed. Radicicol inhibited the secretion of A${\beta}$ from the Neuro2a cell line (APPswe cell) expressing APPswe. Beta-site APP cleaving enzyme (BACE) fluorescence resonance energy transfer (FRET) assay revealed that it inhibited BACE activity in a dose dependently manner. Immunoblotting study showed that it inhibited intracellular heat shock protein (HSP)90 and it increased the secretion of HSP90 from the APPswe cells. We suggest that radicicol inhibits APP metabolism and Ap generation by the means of HSP90 inhibitory mechanism and partially BACE inhibitory mechanism. This is the first report that radicicol inhibits the secretion of A${\beta}$ peptides from neuroblastoma cells.

• 농업과학연구
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• 제46권2호
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• pp.369-379
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• 2019

Alzheimer's disease (AD) is the most common neurodegenerative disease associated with age, and amyloid beta ($A{\beta}$) is known to cause Alzheimer's disease. In the present study, we investigated the protective effects of Cirsium japonicum var. maackii extract and its fractions against $A{\beta}$-induced neurotoxicity in C6 glial cells. The cells treated with $A{\beta}_{25-35}$ showed a decrease in cell viability and an increase in reactive oxygen species (ROS) production compared with the non-treated cells. However, the cells treated with the C. japonicum var. maackii extract and its fractions increased the cell viability and inhibited the $A{\beta}$-induced ROS production. These results demonstrate the neuroprotective effects of C. japonicum var. maackii against $A{\beta}$. To further examine the protective mechanism, we measured inflammation and apoptosis related protein expressions. The cells treated with extract and fractions from C. japonicum var. maackii down-regulated inflammatory related proteins such as cyclooxygenase-2, interleukin $(IL)-1{\beta}$, and IL-6, and attenuated apoptosis related proteins including B-cell lymphoma-2 (Bcl-2) associated X protein/Bcl-2 ratio. In particular, the ethanol and ethylacetate fraction exhibited higher inhibitory effect against ROS production and apoptosis-related protein expressions among the extract and the other fractions. Therefore, this study demonstrated the protective effects of C. japonicum var. maackii extract and its fractions against $A{\beta}$-induced neurotoxicity in C6 glial cells through the regulation of oxidative stress, inflammation, and apoptosis, suggesting that it might have potential as a therapeutic for AD.

• 동의신경정신과학회지
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• 제15권2호
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• pp.103-118
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• 2004

Objective : This experiment was designed to investigate the effect of KongJin-dan(KJD) on the Alzheimer's disease. Method : The effects of KJD on $LI-1{\beta}$, IL-6, $TNF-{\alpha}$, amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 and THP-1 cell treated by CT105 and AChE activity, APP production of PC-12 cell lysate treated by CT105 were investigated, respectively. Results : 1. KJD suppressed $LI-1{\beta}$, IL-6, $TNF-{\alpha}$, APP, AChE, GFAP mRNA in THP-1 and PC-12 cell treated by CT105. 2. KJD suppressed AChE activity and production of APP significantly in cell lysate of PC-12 cell treated by CT105. Conclusions : This study shows that KJD might be usefully applied for prevention and treatment of Alzheimer's disease.

• 동의생리병리학회지
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• 제20권2호
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• pp.394-403
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• 2006

This research investigated the effect of the CMT and MCMT on Alzheimer's disease. The effects of the CMT and MCMT extract on expression of proinflammatory cytokine($IL-1{\beta}$, IL-6, $TNF-{\alpha}$) in the THP-1 cell; amyloid precursor proteins(APP), acetylcholinesterase(AChE) mRNA of PC-12 cells treated with CT105; the AChE activity and the APP production of PC-12 cell lysate treated with CT105 were investigated. The CMT and MCMT extract suppressed overexpression of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ in the THP-1 cell treated by LPS; the expression of APP, AChE mRNA in PC-12 cells treated with CT105; the AChE activity and the production of APP in PC-12 cell lysate treated with CT105 significantly. This study suggest that CMT and MCMT may be effective for the prevention and treatment of Alzheimer's disease.

• 동의생리병리학회지
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• 제20권1호
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• pp.138-148
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• 2006

This research investigated the effect of the CMT and SCMT on Alzheimer's disease. The effects of the CMT and SCMT extract on expression of proinflammatory cytokine(IL-$1{\beta}$, IL-6, TNF-$\alpha$) in the THP-1 cell; amyloid precursor proteins(APP), acetylcholinesterase(AChE) mRNA of PC-12 cells treated with CT105; the AChE activity and the APP production of PC-12 cell lysate treated with CT105 were investigated. The CMT and SCMT extract suppressed overexpression of IL-$1{\beta}$, IL-6, TNF-$\alpha$ in the THP-1 cell treated dy LPS; the expression of APP, AChE mRNA in PC-12 cells treated with CT105; the AChE activity and the production of APP in PC-12 cell Iysate treated with CT105 significantly. This study suggest that CMT and SCMT may be effective for the prevention and treatment of Alzheimer's disease.

• 동의생리병리학회지
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• 제28권3호
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• pp.317-321
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• 2014

Amyloid-${\beta}$ protein ($A{\beta}$) is a pathological component of Alzheimer's disease (AD) by participating in the senile plaque formation in the patient's brain. Although the exact mechanism of $A{\beta}$ toxicity is not fully elucidated, it is considered to be closely related to its fibrillation process. For prevention of AD, recent studies have suggested various small molecules which inhibit $A{\beta}$ fibrillation. In this report, ${\beta}$-asarone found in acorus plant has been investigated as an anti-amyloid molecule. ${\beta}$-Asarone was demonstrated to prevent in vitro fibrillation of $A{\beta}$ by inducing the oligomer formation that obviously decreased cytotoxicity. Therefore, ${\beta}$-asarone could be suggested as an inhibitory agent of $A{\beta}$ fibrillation and toxicity, which would help us not only to understand underlying principle of amyloidogenesis mechanism but also to develop a controlling strategy toward AD.

• 동의신경정신과학회지
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• 제17권1호
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• pp.37-57
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• 2006

Objective : This research investigates the effect of the CMT and MCMT on Alzheimer‘s disease. Methods : The effects of the CMT and MCMT extract on (1) amyloid precursor proteins(APP), acetylcholinesterase(AChE) mRNA of PC-12 cells treated with CT-105; (2) the AChE activity and the APP production of PC-12 cell treated with CT-105; (3) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, GFAP, CD68 abd CD11b; (5) the infarction area of the hippocampus in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. Results : 1. The CMT and MCMT extract suppressed the expression of APP, AChE, and mRNA in PC-12 cells treated with CT-105. 2. The CMT and MCMT extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 3. For the CMT and MCMT extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 4. The CMT and MCMT extract suppressed the over-expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, GFAP, CD68 abd CD11bCD68/GFAP, in the mice with Alzheimer's disease induced by ${\beta}A$. 5. The CMT and MCMT extract reduced the infarction area of hippocampus with Alzheimer's disease induced by ${\beta}A$ 6. The MCMT showed more excellent effects than CMT in the every experiments except PC-12 cells. Conclusions : These results suggest that the CMT and MCMT extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the CMT and MCMT extract for Alzheimer's disease is suggested for future research.

• BMB Reports
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• 제57권6호
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• pp.263-272
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• 2024

Amyloid-β (Aβ) is one of the amyloidogenic intrinsically disordered proteins (IDPs) that self-assemble to protein aggregates, incurring cell malfunction and cytotoxicity. While Aβ has been known to regulate multiple physiological functions, such as enhancing synaptic functions, aiding in the recovery of the blood-brain barrier/brain injury, and exhibiting tumor suppression/antimicrobial activities, the hydrophobicity of the primary structure promotes pathological aggregations that are closely associated with the onset of Alzheimer's disease (AD). Aβ proteins consist of multiple isoforms with 37-43 amino acid residues that are produced by the cleavage of amyloid-β precursor protein (APP). The hydrolytic products of APP are secreted to the extracellular regions of neuronal cells. Aβ 1-42 (Aβ42) and Aβ 1-40 (Aβ40) are dominant isoforms whose significance in AD pathogenesis has been highlighted in numerous studies to understand the molecular mechanism and develop AD diagnosis and therapeutic strategies. In this review, we focus on the differences between Aβ42 and Aβ40 in the molecular mechanism of amyloid aggregations mediated by the two additional residues (Ile41 and Ala42) of Aβ42. The current comprehension of Aβ42 and Aβ40 in AD progression is outlined, together with the structural features of Aβ42/Aβ40 amyloid fibrils, and the aggregation mechanisms of Aβ42/Aβ40. Furthermore, the impact of the heterogeneous distribution of Aβ isoforms during amyloid aggregations is discussed in the system mimicking the coexistence of Aβ42 and Aβ40 in human cerebrospinal fluid (CSF) and plasma.