• Molecules and Cells
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• v.39 no.7
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• pp.543-549
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• 2016

MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. The present study focused on the role of hsa-miR-144-3p in one of the neuro-degenerative diseases, Parkinson's disease (PD). Our study showed a remarkable down-regulation of miR-144-3p expression in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated SH-SY5Y cells. MiR-144-3p was then overexpressed and silenced in human SH-SY5Y cells by miRNA-mimics and miRNA-inhibitor transfections, respectively. Furthermore, ${\beta}$-amyloid precursor protein (APP) was identified as a target gene of miR-144-3p via a luciferase reporter assay. We found that miR-144-3p overexpression significantly inhibited the protein expression of APP. Since mitochondrial dysfunction has been shown to be one of the major pathological events in PD, we also focused on the role of miR-144-3p and APP in regulating mitochondrial functions. Our study demonstrated that up-regulation of miR-144-3p increased expression of the key genes involved in maintaining mitochondrial function, including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$(PGC-$1{\alpha}$), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). Moreover, there was also a significant increase in cellular ATP, cell viability and the relative copy number of mtDNA in the presence of miR-144-3p overexpression. In contrast, miR-144-3p silencing showed opposite effects. We also found that APP overexpression significantly decreased ATP level, cell viability, the relative copy number of mtDNA and the expression of these three genes, which reversed the effects of miR-144-3p overexpression. Taken together, these results show that miR-144-3p plays an important role in maintaining mitochondrial function, and its target gene APP is also involved in this process.

• Korean Journal of Pharmacognosy
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• v.48 no.1
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• pp.31-37
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• 2017

Glutamate-induced oxidative stress results in neuro-degenerative disorders in many central nervous system (CNS) such as Alzheimer's disease, ischemia, Huntington's disease, and Parkinson's disease. Our study was performed to investigate neuroprotective effects of Allium hookeri extracts (leaf, root, and whole) on glutamate-induced HT22 cells. In this study, ethanol extract of A. hookeri showed the outstanding neuroprotective effect in HT22 cells. In addition, we found that ethanol extract of A. hookeri root increased heme oxygenase (HO)-1 in HT22 cells. Moreover, ethanol extract of A. hookeri root also upregulated nuclear accumulation of nuclear factor E2-related factor 2 (Nrf2) in HT22 cells. These results demonstrate that ethanol extract of A. hookeri root contributes neuroprotective effects against glutamate-induced oxidative stress in HT22 cells, via Nrf2-mediated HO-1 expression. Our study suggests that ethanol extract of A. hookeri root could be the potential agent for the treatment of many neuro-degenerative diseases.

• Advances in Traditional Medicine
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• v.10 no.4
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• pp.239-253
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• 2010

Coenzyme $Q_{10}$ ($CoQ_{10}$, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of $CoQ_{10}$ in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit in $CoQ_{10}$ status has been determined in a number of neuromuscular and neurodegenerative disorders. Primary disorders of $CoQ_{10}$ biosynthesis are potentially treatable conditions and therefore a high degree of clinical awareness about this condition is essential. A secondary loss of $CoQ_{10}$ status following HMG-CoA reductase inhibitor (statins) treatment has been implicated in the pathophysiology of the myotoxicity associated with this pharmacotherapy. $CoQ_{10}$ and its analogue, idebenone, have been widely used in the treatment of neurodegenerative and neuromuscular disorders. These compounds could potentially play a role in the treatment of mitochondrial disorders, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Friedreich's ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of $CoQ_{10}$, as well as the rationale and the role in clinical practice of $CoQ_{10}$ supplementation in different neurological diseases, from primary $CoQ_{10}$ deficiency to neurodegenerative disorders. These will help in future for treatment of patients suffering from neurodegenerative disease.

• Korean Journal of Pharmacognosy
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• v.42 no.3
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• pp.276-281
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• 2011

Oxidative stress or the accumulation of reactive oxygen species (ROS) leads neuronal cellular death and dysfunction, and it contributes to neuronal degenerative disease such as Alzheimer's disease, Parkinson's disease and stroke. Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as epilepsy and ischemia. Heme oxygenase-1 (HO-1) enzyme plays an important role of cellular antioxidant system against oxidant injury. The expression of HO-1 has cytoprotective effects in glutamate-induced oxidative cytotoxicity in HT22 cells. The induction of HO-1 is primarily regulated at the transcriptional level, and its induction by various inducers is related to the nuclear transcription factor-E2-related factor 2 (Nrf2). Nrf2 is a master regulator of the antioxidant response. NNMBS008, the water-insoluble fraction of the 70% EtOH extract of roots of Sophora flavescens, showed dominant neuroprotective effects on glutamate-induced neurotoxicity in mouse hippocampal HT22 cells by induced the expression of HO-1 and increased HO activity. In mouse hippocampal HT22 cells, NNMBS008 makes the nuclear accumulation of Nrf2 pathway. In conclusion, the waterinsoluble fraction of the 70% EtOH extract of roots of S. flavescens (NNMBS008) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 pathway in mouse hippocampal HT22 cells. These results suggest that these extracts could be the effective candidates for the treatment of ROS-related neurological diseases.

• Journal of Oriental Neuropsychiatry
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• v.10 no.1
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• pp.53-78
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• 1999

As the average life span have been lengthened and the rate of senile population have been raised, chronic degenerative diseases incident to aging has been increased rapidly and become a social problem. With this social background, recently, the facts that oxygen radicals(OR) have toxic effects on Central Nervous System and Peripheral Nervous System and cause neuropathy such as Parkinson's Disease, Alzheimer Disease have been turned out, and accordingly lots of studies on the mechanism of the toxic effects of OR on nerves, the diseases caused by OR and the approaches to curing the diseases have been made. The purpose of this study is to examine the toxic effects caused by Glucose Oxidase(GO) and the effects of herbal extracts such as Chilbokyeum(CBY), Chilbokyeumga Acori Rhizoma(CAR), Acori Rhizoma(AR) on the treatment of the toxic effects. For this purpose, experiments with the cultured cell from the cerebrums of new born mice were done. The results of these experiments were as follows. 1. GO, a oxygen radical, decreased the survival rate of the cultured cells on NR assay, MTT assay and amount of neurofilaments and increased the amount of total protein, lipid peroxidation and the amount of LDH. 2. CBY have efficacy of increasing the amount of neurofilaments and total protein and decreasing lipid peroxidation and the amount of LDH. 3. CAR have efficacy of increasing the amount of neurofilaments and total protein and decreasing lipid peroxidation and the amount of LDH. 4. AR have efficacy of increasing the amount of neurofilaments and total protein. From the above results, It is concluded that Chilbokyeumgamibang has marked efficacy as a treatment for the damages caused in the GO-mediated oxidative process. And Chilbokyeumgamibang is thought to have certain pharmacological effects on controlling over aging and treating Dementia. Further clinical study of this pharmacological effects of Chilbokyeumgamibang should be complemented.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.210-217
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• 2018

Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer's disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3',4'-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3',4'-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin $E_2$ and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor $(NF)-{\kappa}B$ activation. This indicates that the anti-inflammatory activities of 3',4'-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and $NF-{\kappa}B$ signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3',4'-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.

• Korean Journal of Radiology
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• v.24 no.3
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• pp.247-258
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• 2023

Objective: To localize the neuroanatomical substrate of rapid eye movement sleep behavior disorder (RBD) and to investigate the neuroanatomical locational relationship between RBD and α-synucleinopathy neurodegenerative diseases. Materials and Methods: Using a systematic PubMed search, we identified 19 patients with lesions in different brain regions that caused RBD. First, lesion network mapping was applied to confirm whether the lesion locations causing RBD corresponded to a common brain network. Second, the literature-based RBD lesion network map was validated using neuroimaging findings and locations of brain pathologies at post-mortem in patients with idiopathic RBD (iRBD) who were identified by independent systematic literature search using PubMed. Finally, we assessed the locational relationship between the sites of pathological alterations at the preclinical stage in α-synucleinopathy neurodegenerative diseases and the brain network for RBD. Results: The lesion network mapping showed lesions causing RBD to be localized to a common brain network defined by connectivity to the pons (including the locus coeruleus, dorsal raphe nucleus, central superior nucleus, and ventrolateral periaqueductal gray), regardless of the lesion location. The positive regions in the pons were replicated by the neuroimaging findings in an independent group of patients with iRBD and it coincided with the reported pathological alterations at post-mortem in patients with iRBD. Furthermore, all brain pathological sites at preclinical stages (Braak stages 1-2) in Parkinson's disease (PD) and at brainstem Lewy body disease in dementia with Lewy bodies (DLB) were involved in the brain network identified for RBD. Conclusion: The brain network defined by connectivity to positive pons regions might be the regulatory network loop inducing RBD in humans. In addition, our results suggested that the underlying cause of high phenoconversion rate from iRBD to neurodegenerative α-synucleinopathy might be pathological changes in the preclinical stage of α-synucleinopathy located at the regulatory network loop of RBD.

• Speech Sciences
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• v.12 no.3
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• pp.19-33
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• 2005

Tremor is a main factor of parkinsonism. Voice tremor may be the first, later or the only symptom of a neurological disease and its frequency, amplitude, and regularity may differ among the diseases of different neural subsystems. Differential diagnosis between idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA) has been difficult. This study included three groups: (1) 6 IPD patients; (2) 6 MSA patients; and (3) 20 ageand sex-matched normal controls. The MDVP (Multidimensional Voice Program) was used to analyze the sustained /a/phonation. The results were as follows: (1) frequency perturbation parameters (jitter, sPPQ, Vf0) and FTRI of tremor parameter of two patient groups were statistically different from those of the controls (p < .01); (2) measures were higher in short-term and long-term f0 and amplitude perturbation in MSA than IPD; (3) however, any acoustic parameters between IPD and MSA were not statistically different; except for the rate of frequency tremor, 4$\sim$5 Hz in IPD, 5$\sim$11 Hz in MSA and (4) the pattern of regularity for voice tremor through histogram indicated that amplitude of IPD was irregular while both f0 and amplitude of MSA were irregular. In conclusion, F0, rate of frequency tremor, and pattern of f0 regularity may be predictors for differential diagnosis. These findings might signify that voice tremor of parkinsonism was resulted from modulation of f0.

• Journal of Korean Neurosurgical Society
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• v.62 no.1
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• pp.10-26
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• 2019

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer's disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.276-284
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• 2023

Sinapic acid (SA) is a phenolic acid that is widely distributed in fruits and vegetables, which has various bioactivities, such as antidiabetic, anticancer and anti-inflammatory functions. Over-activated microglial is involved in the development progress of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. The objective of this study was to investigate the effect of SA in microglia neuroinflammation models. Our results demonstrated that SA inhibited secretion of the nitric oxide (NO) and interleukin (IL)-6, reduced the expression of inducible nitric oxide synthase (iNOS) and enhanced the release of IL-10 in a dose-dependent manner. Besides, our further investigation revealed that SA attenuated the phosphorylation of AKT and MAPK cascades in LPS-induced microglia. Consistently, oral administration of SA in mouse regulated the production of inflammation-related cytokines and also suppressed the phosphorylation of MAPK cascades and AKT in the mouse cerebral cortex. These results suggested that SA may be a possible therapy candidate for anti-inflammatory activity by targeting the AKT/MAPK signaling pathway.