• YAKHAK HOEJI
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• v.60 no.2
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• pp.92-99
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• 2016

Parkinson's disease (PD) is one of the representative neurodegenerative movement disorders with the selective loss of dopaminergic neurons in the substantia nigra. 6-Hydroxydopamine (6-OHDA) is widely used as an experimental model system to mimic PD and has been reported to cause neuronal cell death via oxidative and/or nitrosative stress. Therefore, daily intake of dietary or medicinal plants which fortifies cellular antioxidant capacity can exert neuroprotective effects in PD. In the present study, we have investigated the protective effect of Korean red ginseng (KRG) against 6-OHDA-induced nitrosative death in C6 glioma cells. Treatment of C6 cells with 6-OHDA decreased cell viability and increased expression of inducible nitric oxide synthase, production of nitric oxide as well as peroxynitrite, and formation of nitrotyrosine. 6-OHDA led to apoptotic cell death as determined by decreased Bcl-2/Bax, phosphorylation of JNK, activation of caspase-3, and cleavage of PARP. Conversely, pretreatment of C6 cells with KRG attenuated 6-ODHA-induced cytotoxicity, apoptosis, and nitrosative damages. To further elucidate the molecular mechanism of KRG protection against 6-OHDA-induced nitrosative cell death, we have focused on the cellular self-defense molecules against exogenous noxious stimuli. KRG treatment up-regulated heme oxygenase-1 (HO-1), a key antioxidant enzyme essential for cellular defense against oxidative and/or nitrosative stress via activation of Nrf2. Taken together, these findings suggest KRG may have preventive and/or therapeutic potentials for the management of PD.

• Korean Journal of Acupuncture
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• v.32 no.3
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• pp.108-115
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• 2015

Objectives : Acupuncture is frequently used as an alternative therapy for Parkinson's disease(PD) in Korea. Using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease mouse model, the present study investigated a possible role of acupuncture stimulation at GB34 in suppressing dopaminergic neuronal death and regulating the phosphorylation of protein kinase B(Akt) in substantia nigra(SN) and striatum(ST). Methods : Eight-week-old male C57BL/6 mice were administered intraperitoneally with 30 mg/kg of MPTP at 24-h intervals for 5 days. Acupuncture stimulation at GB34 or SI3 was performed once a day for 12 days consecutively from the first MPTP injection. After the last acupuncture stimulation, pole test was performed to assess the effect of the acupuncture stimulations. Dopaminergic neuronal survival in the SN and the ST, dopamine transporter( DAT) and caspase-3 expression in the ST were evaluated by immunohistochemistry. The phosphorylations of Akt in the SN and the ST were measured by Western blotting. Results : MPTP administration caused behavioral impairment and dopaminergic neuronal death in the SN and the ST. It also decreased DAT expression and increased caspase-3 expression in the ST. Acupuncture stimulation at GB34 alleviated these MPTP-induced impairments. Moreover, MPTP suppressed Akt phosphorylation in the SN and the ST, whereas acupuncture stimulation at GB34 alleviated the phosphorylation in the SN. Conclusions : These results indicate that acupuncture stimulation at GB34 can inhibit MPTP-induced dopaminergic neuronal death and alleviate the Akt phosphorylation in the SN, suggesting a possible role for acupuncture in the treatment of PD.

• Journal of the Korean Society of Tobacco Science
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• v.19 no.2
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• pp.136-144
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• 1997

Cigarette smoking is known to suppress both 1-methy14-phenyl-155,Ltetrahydropy-ridine (MPTP)-induced parkinsonism and idiopathic Parkinson's disease (PD). However, the precise mechanism underlying its protective action against PD is not clearly elucidated yet. In order to find possible clue on the mechanism of protective action of smoking, we investigated the inhibitory effect of cigarette smoke components on rat brain mitochondria1 monoamine oxidase B (MAO-B), responsible enzyme for the activation of MPTP to its toxic metabolitesr and identified the components having an inhibitory potency on this enzyme from cigarette smoke. Total 31 eligible constituents including nicotine were selected from cigarette smoke condensates via solvents partitioning and silica gel chromatographic separation, and inhibitory potencies of 19 components on MAO-B were determined. Hydroquinone and methylcatechol, the phenolic components, showed the strongest inhibitory potencies on MAO-B activity in the components tested. 3,4-Dihydroxybenzylamino, myosmine and indole in basic fracton, eugenol in phenolic fraction, and farnesol in neutral fraction also inhibited the enzyme activity dose-dependently. Among tobacco alkaloids tested only myosmine was effective for the inhibition of this enzyme. These results suggest that the decrease in MAO-B activity by such components derived from cigarette smoke seems to be related to the suppression of MPTP-induced neurotoxicity and to the less incidence of Parkinson's disease in smokers than in nonsmokers.

• Molecules and Cells
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• v.40 no.7
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• pp.450-456
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• 2017

Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm. Specifically, genetic deletion of the circadian nuclear receptor Rev-$erb{\alpha}$ induces mania-like behavior caused by increased midbrain dopaminergic (DAergic) tone at dusk. The association between circadian rhythm and emotion-related behaviors can be applied to pathological conditions, including neurodegenerative diseases. In Parkinson's disease (PD), DAergic neurons in the substantia nigra pars compacta progressively degenerate leading to motor dysfunction. Patients with PD also exhibit non-motor symptoms, including sleep disorder and neuropsychiatric disorders. Thus, it is important to understand the mechanisms that link the molecular circadian clock and brain machinery in the regulation of emotional behaviors and related midbrain DAergic neuronal circuits in healthy and pathological states. This review summarizes the current literature regarding the association between circadian rhythm and mood regulation from a chronobiological perspective, and may provide insight into therapeutic approaches to target psychiatric symptoms in neurodegenerative diseases involving circadian rhythm dysfunction.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.363-372
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• 2019

Daidzein isolated from soybean (Glycine max) has been widely studied for its antioxidant and anti-inflammatory activities. However, the protective effects of 7,8,4'-trihydroxyisoflavone (THIF), a major metabolite of daidzein, on 6-hydroxydopamine (OHDA)-induced neurotoxicity are not well understood. In the current study, 7,8,4'-THIF significantly inhibited neuronal cell death and lactate dehydrogenase (LDH) release induced by 6-OHDA in SH-SY5Y cells, which were used as an in vitro model of Parkinson's disease (PD). Moreover, pretreatment with 7,8,4'-THIF significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) and decreased malondialdehyde (MDA) activity in 6-OHDA-induced SH-SY5Y cells. In addition, 7,8,4'-THIF significantly recovered 6-OHDA-induced cleaved caspase-3, cleaved caspase-9, cleaved poly-ADP-ribose polymerase (PARP), increased Bax, and decreased Bcl-2 levels. Additionally, 7,8,4'-THIF significantly restored the expression levels of phosphorylated c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK 1/2), phosphatidylinositol 3-kinases (PI3K)/Akt, and glycogen synthase kinase-3 beta ($GSK-3{\beta}$) in 6-OHDA-induced SH-SY5Y cells. Further, 7,8,4'-THIF significantly increased the reduced tyrosine hydroxylase (TH) level induced by 6-OHDA in SH-SY5Y cells. Collectively, these results suggest that 7,8,4'-THIF protects against 6-OHDA-induced neuronal cell death in cellular PD models. Also, these effects are mediated partly by inhibiting activation of the MAPK and PI3K/Akt/$GSK-3{\beta}$ pathways.

• The Korea Journal of Herbology
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• v.28 no.5
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• pp.21-28
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• 2013

Objectives : The aim of this study was to investigate the neuroprotective effects and mechanisms of Cyperi Rhizoma extracts (CRE) using in vitro and in vivo models of Parkinson's disease (PD). Methods : We evaluated the neuroprotective effect of CRE against 1-methyl-4-phenylpyridinium (MPP+) toxicity using tyrosine hydroxylase immunohistochemistry (IHC) in primary rat mesencephalic dopaminergic neurons. In addition, the effect of CRE was evaluated in mice PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). For evaluations, C57bl/6 mice were orally treated with CRE 50 mg/kg for 5 days and were injected intraperitoneally with MPTP (20 mg/kg) at 2 h intervals on the last day. To identify the CRE affects on MPTP-induced neuronal loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and striatum of mice, the behavioral tests and IHC analysis were carried out. Also, we conducted nitric oxide (NO) and tumor necrosis factor-alpha (TNF-${\alpha}$) assay in dopaminergic neurons and IHC using glial markers in SNpc of mice to assess the anti-inflammation effects. Results : In primary mesencephalic culture system, CRE protected dopaminergic cells against $10{\mu}M$ MPP+-induced toxicity at 0.2 and $1.0{\mu}g/mL$. In the behavior tests, CRE treated group showed improved motor deteriorations than those in the MPTP only treated group. CRE significantly protected striatal dopaminergic damage from MPTP-induced neurotoxicity in mice. Moreover, CRE inhibited productions of NO and TNF-${\alpha}$ in dopaminergic culture system and activation of astrocyte and microglia in SNpc of the mice. Conclusion : We concluded that CRE shows anti-parkinsonian effect by protecting dopaminergic neurons against MPP+/MPTP toxicities through anti-inflammatory actions.

• BMB Reports
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• v.57 no.8
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• pp.363-368
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• 2024

Parkinson's disease (PD), characterized by dopaminergic neuron degeneration in the substantia nigra, is caused by various genetic and environmental factors. Current treatment methods are medication and surgery; however, a primary therapy has not yet been proposed. In this study, we aimed to develop a new treatment for PD that induces direct reprogramming of dopaminergic neurons (iDAN). Achaete-scute family bHLH transcription factor 1 (ASCL1) is a primary factor that initiates and regulates central nervous system development and induces neurogenesis. In addition, it interacts with BRN2 and MYT1L, which are crucial transcription factors for the direct conversion of fibroblasts into neurons. Overexpression of ASCL1 along with the transcription factors NURR1 and LMX1A can directly reprogram iDANs. Using a retrovirus, GFP-tagged ASCL1 was overexpressed in astrocytes. One week of culture in iDAN convertsion medium reprogrammed the astrocytes into iDANs. After 7 days of differentiation, TH+/TUJ1+ cells emerged. After 2 weeks, the number of mature TH+/TUJ1+ dopaminergic neurons increased. Only ventral midbrain (VM) astrocytes exhibited these results, not cortical astrocytes. Thus, VM astrocytes can undergo direct iDAN reprogramming with ASCL1 alone, in the absence of transcription factors that stimulate dopaminergic neurons development.

• Journal of Life Science
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• v.32 no.10
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• pp.771-777
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• 2022

Dopaminergic (DA) cell death in Parkinson's disease (PD) has been attributed to multiple, distinct genetic and environmental factors. In rare familial PD loss of parkin function mutations play a key role in nigral DA neuron-specific pathogenesis primarily via endoplasmic reticulum (ER) stress. In more prevalent sporadic PD, environmental exposure to pesticides has a significant epidemiological role. However, it is largely unknown how environmental exposure to xenobiotics is etiologically linked with the known etiology in familial PD. In the present study biochemical evidence for a common pathogenic mechanism between sporadic and familial PD has been identified employing the recently characterized mesencephalic DA cell line, N27-A. Dieldrin, an organochlorine pesticide epidemiologically implicated in sporadic PD, induced the markers of ER stress response such as a chaperone BiP/Grp78, heme oxygenase-1 and especially, parkin. Accordingly, dieldrin activated the ER resident Caspase-12, a mediator of ER stress-specific apoptosis, during cell death of N27-A cells. Of great interest the dieldrin-induced DA neuronal cell death was synergistically rescued by the overexpression of ER resident neuroprotective proteins, parkin and Bcl-2. The present findings implicate that accumulation of ER stress could be one of common pathogenic mechanisms in idiopathic and familial PD, and some ER proteins, such as parkin and Bcl-2 may effectively attenuate ER stress-mediated N27-A DA cell death.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1041-1045
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• 2015

Background: Paget's disease (PD) is a rare form of intraepithelial adenocarcinoma that involves breast and extramammarian tissues. It is often associated with ductal carcinoma in situ and/or invasive ductal cancer. Molecular pathways that play a role in development of Paget's disease are stil unclear. Expression patterns of Cox-2 and bcl-2 were therefore assessed. Materials and Methods: Patients with a histopathological diagnosis of Paget's disease were included in this study. Patient files were analysed retrospectively. Results: Invasive cancer was diagnosed in 35 (76.1%) of the patients, 7 (15.2%) had ductal carcinoma in situ and 4 (8.7%) patients had no associated neoplasm. Twenty four (52.2%) patients showed COX-2 expression in Paget cells whereas no expression was seen in 22 (47.8%) patients. No relation was found between COX-2 expression and the lesion underlying Paget's disease (p=0.518). Bcl-2 expression in Paget cells was found positive in 12 (26.1%) and negative in 27 (58,7%) cases. There was no relation between Bcl-2 expression and the lesion accompanying Paget's disease (p=0.412). No relation was observed between COX-2 expression and Bcl-2 expression (p=0.389). Conclusions: In breast cancer, COX-2 expression is associated with poor prognostic factors. As COX-2 expression increases the tendency to metastasize also increases. In our study we found a significantly high COX-2 expression in Paget's disease of the breast. We suggest that COX-2 expression and inflammatory processes may play a role in pathogenesis of the Paget's disease of the breast.

• Journal of the Korean Society of Physical Medicine
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• v.10 no.2
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• pp.55-61
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• 2015

PURPOSE: The purpose of this study was to investigate recruiting order and onset time around shoulder muscle during the push-up according to the body tilting angle. METHODS: Twenty healthy young adult subjects were recruited for this study. They had no neurological and musculoskeletal disease. We used the sEMG for recording onset time of shoulder muscles. Shoulder Muscles were anterior deltoid(AD), posterior deltoid(PD), pectoralis major(PM), upper trapezius(UT). Body tilting angle were measured at 0 degree, 30 degree and 60 degree by using tilting table. Muscles contraction onset time were set by the push-up performed 3 times respectively. Mean of 3 measurements were used. And initiate onset time was decided by the Mean ${\pm}2$ SD in the threshold, more than 25ms. RESULTS: There were significant difference at 0 degree, 30 degree and 60 degree(p<.05). Muscles onset time were same order at 0 degree, 30 degree. UT occurred first of all contraction at 0 degree and 30 degree. And then contracted AD, PD, PM. But, at 60 degree, AD was the first contraction, and PM, UT, PD. CONCLUSION: Muscle recruitment order and onset time according to the body tilting was shown the difference when you do push-up. Therefore, this result, shoulder muscle recruitment pattern of according to the body tilting is different and it has to make effective shoulder exercise program.