• Molecules and Cells
• /
• v.46 no.4
• /
• pp.191-199
• /
• 2023

The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of the Golgi apparatus, including vesicle trafficking and the post-translational modification of macromolecules. These proteins are not modified or delivered appropriately due to the insufficiency in the Golgi function. These conditions disturb Golgi homeostasis and induce a cellular condition known as Golgi stress, causing cells to activate the 'Golgi stress response,' which is a homeostatic process to increase the capacity of the Golgi based on cellular requirements. Since the Golgi functions are diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ETS, and PERK regulate the capacity of each Golgi function separately. Understanding the Golgi stress response is crucial for revealing the mechanisms underlying Golgi dynamics and its effect on human health because many signaling molecules are related to diseases, ranging from viral infections to fatal neurodegenerative diseases. Therefore, it is valuable to summarize and investigate the mechanisms underlying Golgi stress response in disease pathogenesis, as they may contribute to developing novel therapeutic strategies. In this review, we investigate the perturbations and stress signaling of the Golgi, as well as the therapeutic potentials of new strategies for treating Golgi stress-associated diseases.

• Biomolecules & Therapeutics
• /
• v.32 no.3
• /
• pp.301-308
• /
• 2024

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by extracellular amyloid plaques composed of amyloid β-peptide (Aβ). Studies have indicated that Ca²⁺ dysregulation is involved in AD pathology. It is reported that decreased capacitative Ca²⁺ entry (CCE), a refilling mechanism of intracellular Ca²⁺, resulting in increased Aβ production. In contrast, constitutive activation of CCE could decrease Aβ production. Panax ginseng Meyer is known to enhance memory and cognitive functions in healthy human subjects. We have previously reported that some ginsenosides decrease Aβ levels in cultured primary neurons and AD mouse model brains. However, mechanisms involved in the Aβ-lowering effect of ginsenosides remain unclear. In this study, we investigated the relationship between CCE and Aβ production by examining the effects of various ginsenosides on CCE levels. Aβ-lowering ginsenosides such as Rk1, Rg5, and Rg3 potentiated CCE. In contrast, ginsenosides without Aβ-lowering effects (Re and Rb2) failed to potentiate CCE. The potentiating effect of ginsenosides on CCE was inhibited by the presence of 2-aminoethoxydiphenyl borate (2APB), an inhibitor of CCE. 2APB alone increased Aβ42 production. Furthermore, the presence of 2APB prevented the effects of ginsenosides on Aβ42 production. Our results indicate that ginsenosides decrease Aβ production via potentiating CCE levels, confirming a close relationship between CCE levels and Aβ production. Since CCE levels are closely related to Aβ production, modulating CCE could be a novel target for AD therapeutics.

• Dementia and Neurocognitive Disorders
• /
• v.23 no.2
• /
• pp.75-88
• /
• 2024

The Korean Dementia Association (KDA) has been organizing biennial international academic conferences since 2019, with the International Conference of the KDA (IC-KDA) 2023 held in Busan under the theme 'Beyond Boundaries: Advancing Global Dementia Solutions.' The conference comprised 6 scientific sessions, 3 plenary lectures, and 4 luncheon symposiums, drawing 804 participants from 35 countries. Notably, a Korea-Taiwan Joint Symposium addressed insights into Alzheimer's disease (AD). Plenary lectures by renowned scholars explored topics such as microbiome-related AD pathogenesis, social cognition in neurodegenerative diseases, and genetic frontotemporal dementia (FTD). On the first day, specific presentations covered subjects like the gut-brain axis and neuroinflammation in dementia, blood-based biomarkers in AD, and updates in AD therapeutics. The second day's presentations addressed recent issues in clinical neuropsychology, FTD cohort studies, and the pathogenesis of non-AD dementia. The Academic Committee of the KDA compiles lecture summaries to provide comprehensive understanding of the advanced dementia knowledge presented at IC-KDA 2023.

• Journal of Life Science
• /
• v.26 no.5
• /
• pp.509-518
• /
• 2016

Asparagus cochinchinensis is a medical plant that has long been used to treat fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease in northeast Asian countries. Although several studies have been conducted on the anti-neuroinflammatory effects of A. cochinchinensis, the correlation between these effects and nerve growth factor (NGF) has not yet been examined. In this study, we investigated the effects of an aqueous extract of A. cochinchinensis (AEAC) on the secretion and action mechanism of NGF in neuronal cells. The concentration of the NGF protein in the supernatant collected from cultured cells increased significantly in B35 cells treated with AEAC in comparison with the vehicle-treated group without any specific cytotoxicity. Furthermore, the mRNA expression of NGF showed a very similar pattern to its protein concentration. To examine the bioactivity of NGF secreted from B35 cells, undifferentiated PC12 cells were cultured in an AEAC-conditioned medium and neuritic outgrowth was observed. The dendrite length of PC12 cells in the AEAC-treated group was significantly higher than that in the vehicle-treated group. Moreover, the level of the downstream effectors p-TrkA and p-ERK of the high-affinity NGF receptor was significantly higher in the AEAC-treated group, while the expression of the downstream effectors of the low-affinity NGF receptor was significantly lower in the same group. These results suggest that AEAC may contribute to the regulation of NGF expression and secretion in neuronal cells; it is therefore an excellent candidate for further investigation as a therapeutic drug for neurodegenerative diseases.

• Journal of Life Science
• /
• v.30 no.4
• /
• pp.331-342
• /
• 2020

The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.

• Korean Journal of Medicinal Crop Science
• /
• v.18 no.5
• /
• pp.291-297
• /
• 2010

Liriope platyphylla has been though as an useful medical plant to improve the cough, sputum, neurodegenerative disorders, obesity, and diabetes in Korea and China from old times. In order to investigate the effects of Liriope platyphylla on expression and secretion of nerve growth factor (NGF), the mRNA expression and protein secretion were detected in the neuronal cell (B35) and neuroglial cell (C6) cultured with three differences concentration (5%, 10%, 15%) of Liriope platyphylla. In MTT assay and FACS anslysis, the some death of some B35 and C6 cells were observed in 15% extract-treated group, while other groups did not induce the death. Also, the mRNA expression of NGF were significantly increased in 5% and 10% extracts treated-group. Furthermore, the NGF protein concentration in supernatant collected from cultured cells showed the very similar pattern with mRNA expression. In order to verify the activity of secreted NGF, the culture supernatant collected from B35 and C6 cells cultured with Liriope platyphylla extracts for 24 hrs were treated into undifferentiated PC12 cells, and the differentiation level of PC12 cell were also observed with microscopes. The differentiation level of PC12 cell were significantly increased depend on the dose of extract. Therefore, these results suggested that the water extracts of Liriope platyphylla may contribute the regulation of NGF expression and secretion in the neuronal cell and be considered as an excellent candidate for a neurodegenerative disease-therapeutic drug.

• Journal of the Korean Child Neurology Society
• /
• v.23 no.2
• /
• pp.45-50
• /
• 2015

Purpose: X-linked adrenoleukodystrophy (X-ALD) is a fatal, axonal demyelinating, neurodegenerative disease, and is caused by mutations the in ABCD1 (ATP-binding cassette transporter subfamily D member 1). Oxidative damage of proteins caused by very long chain fatty acid accumulating in X-ALD, is an early event in the neurodegenerative cascade. We evaluated valproic acid (VPA) as a possible option for oxidative damage in X-ALD. Method: We generated fibroblast of the childhood cerebral ALD from patient. We evaluated mRNA (ribonucleic acid) level of ABCD2 by real-time polymerase chain reaction, and reactive oxygen species (ROS) levels by flow cytometry. Results: VPA increased expression of ABCD2 in both control and ALD fibroblast. ABCD2 gene mRNA expression was increased 1.76 fold in normal fibroblasts, and 2.22 fold in the X-ALD fibroblasts. ROS levels were decreased in VPA treated X-ALD fibroblast, especially in treated with 1 mM of VPA. ROS levels revealed 13.7 in control fibroblast, on the other hand, 5.83 in X-ALD fibroblast treated with 1 mM of VPA. Conclusion: We propose VPA as a promising novel therapeutic approach in oxidant damage that warrants further clinical investigation in X-ALD.

• Journal of Digital Convergence
• /
• v.17 no.8
• /
• pp.265-270
• /
• 2019

Growing evidence suggests that mediating apoptotic cell death of ER stress plays an important role in pathological development of neurodegenerative diseases including Alzheimer's disease. The ethanol extract of Rodiola sacra (ERS) investigates whether ER stress protects neuroinvasive neuro-2A cells from homocysteine (Hcy) cell death and ER stress. In neuronal cells, Hcy markedly decreased the viability of the cells and induced the death of Annexin V-positive cells as confirmed by MTT assay. The Hcy cell viability and apoptotic loss pretreated with ERS were attenuated, and Hcy showed stress in the expression of C / EBP homologous protein, 78-kDa glucose regulatory protein and the junction of X-box binding protein-1 (xbp1) mRNA. ESR decreased Hcy-induced mRNA binding, GRP78 and CHOP cells induced Hcy-induced ER stress and apoptosis, and Western blotting revealed expression of heme oxygenase-1 and HO-1 enzyme activity Inhibition is indicative of therapeutic value for neurodegenerative diseases such as decreased cell death by hemin.

• Journal of the Korean Dietetic Association
• /
• v.27 no.4
• /
• pp.248-262
• /
• 2021

This study examined the effect of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet of the Korean multi-domain dementia prevention program on the cognitive functions of the elderly with dementia risk factors. We developed the program including nutrition, exercise, cognitive training, vascular disease prevention, and motivation. One- hundred and fifty-three participants aged 60~79 years with at least 1 dementia risk factor were randomly assigned in a 1:1:1 ratio to the facility-based intervention (FMI), home-based intervention (HMI), and the control group. The nutrition education program consisted of 10 classes over 24 weeks: the FMI received 7 group sessions and three 1:1 sessions, the HMI received 4 group sessions and three 1:1 sessions with 3 homework sessions. The Nutrition Quotient for Elderly (NQ-E) and the Mini Nutritional Assessment (MNA) were used to evaluate nutritional status. The Repeatable Battery for the Assessment Neuropsychological Status (RBANS), Korean Mini-Mental State Examination (K-MMSE), and the Cognitive Complaint Interview (CCI) were used to evaluate cognitive functions. A total of 136 people completed the program with an 11.1% dropout rate. The NQ-E (P=0.009) and RBANS (P=0.001) scores significantly increased in the FMI (N=45) and HMI (N=49) groups compared to the control group (N=42) after the study. The changes in the score of MNA and CCI did not differ significantly between groups. In conclusion, the nutritional intervention which focused on the MIND diet as a part of a multi-domain intervention program had a positive effect on the improvement of healthy eating habits and cognitive function scores in the high-risk dementia group.

• The Korea Journal of Herbology
• /
• v.27 no.6
• /
• pp.131-137
• /
• 2012

Objectives : Cyclooxygenase (COX) plays a central role in the inflammatory cascade by converting arachidonic acid into prostaglandin. COX-2 is typically induced by inflammatory stimuli in the majority of tissues, it is responsible for propagating the inflammatory response and thus, considered as the best target for anti-inflammatory drugs. The present study investigated the modulatory effect of ginsenoside Rg3, a principle active ingredient in Panax ginseng, on COX-2 expression in the brain tissue induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Methods : Because systemic LPS treatment induces COX-2 expression immediately in the brain, ginsenoside Rg3 was treated orally with doses of 10, 20, and 30 mg/kg at 1 hour before the LPS (3 mg/kg, i.p.) injection. At 4 hours after the LPS injection, COX-2 mRNA was measured by real-time polymerase chain reaction method, COX-2 protein levels were measured by Western blotting. In addition, COX-2 expressions in brain tissue were observed with immunohistochemistry and double immunofluoresence labeling. Results : Ginsenoside Rg3 (20 and 30 mg/kg) significantly attenuates up-regulation of COX-2 mRNA and protein expression in brain tissue at 4 hours after the LPS injection. Moreover, ginsenoside Rg3 (20 mg/kg) significantly reduced the number of COX-2 positive neurons in the cerebral cortex and amygdala. Conclusion : These results indicate that ginsenoside Rg3 plays a modulatory role in neuroinflammation through the inhibition of COX-2 expression in the brain and suggest that ginsenoside Rg3 and ginseng may be effective on neurodegenerative diseases caused by neuroinflammation.