• Title/Summary/Keyword: brain diseases

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Ribosomal Protein L19 and L22 Modulate TLR3 Signaling

  • Yang, Eun-Jeong;Seo, Jin-Won;Choi, In-Hong
    • IMMUNE NETWORK
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    • v.11 no.3
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    • pp.155-162
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    • 2011
  • Background: Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA) and induces inflammation. In this study we attempted to ascertain if there are endogenous host molecules controlling the production of cytokines and chemokines. Two candidates, ribosomal protein L19 and L22, were analyzed to determine if they influence cytokine production followed by TLR3 activation. In this study we report that L19 acts upon production of IP-10 or IL-8 differently in glioblastoma cells. Methods: L19 or L22 was transfected into HEK293-TLR3, A549 or A172 cells. After treatment with several inhibitors of NF-${\kappa}B$, PI3K, p38 or ERK, production of IL-8 or IP-10 was measured by ELISA. siRNA was introduced to suppress expression of L19. After Vesicular stomatitis virus infection, viral multiplication was measured by western blot. Results: L19 increased ERK activation to produce IL-8. In A172 cells, in which TLR3 is expressed at endosomes, L19 inhibited interferon regulatory factor 3 (IRF3) activation and IP-10 production to facilitate viral multiplication, whereas L19 inhibited viral multiplication in A549 cells bearing TLR3 on their cell membrane. Conclusion: Our results suggest that L19 regulates TLR3 signaling, which is cell type specific and may be involved in pathogenesis of autoimmune diseases and chronic inflammatory diseases.

Tutorial on Drug Development for Central Nervous System

  • Yoon, Hye-Jin;Kim, Jung-Su
    • Interdisciplinary Bio Central
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    • v.2 no.4
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    • pp.9.1-9.5
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    • 2010
  • Many neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, are devastating disorders that affect millions of people worldwide. However, the number of therapeutic options remains severely limited with only symptomatic management therapies available. With the better understanding of the pathogenesis of neurodegenerative diseases, discovery efforts for disease-modifying drugs have increased dramatically in recent years. However, the process of translating basic science discovery into novel therapies is still lagging behind for various reasons. The task of finding new effective drugs targeting central nervous system (CNS) has unique challenges due to blood-brain barrier (BBB). Furthermore, the relatively slow progress of neurodegenerative disorders create another level of difficulty, as clinical trials must be carried out for an extended period of time. This review is intended to provide molecular and cell biologists with working knowledge and resources on CNS drug discovery and development.

Dexamethasone Downregulates Expressions of 14-3-3β and γ-Isoforms in Mice with Eosinophilic Meningitis Caused by Angiostrongylus cantonensis Infection

  • Tsai, Hung-Chin;Chen, Yu-Hsin;Yen, Chuan-Min;Chung, Li-Yu;Wann, Shue-Ren;Lee, Susan Shin-Jung;Chen, Yao-Shen
    • Parasites, Hosts and Diseases
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    • v.57 no.3
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    • pp.249-256
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    • 2019
  • Steroids are commonly used in patients with eosinophilic meningitis caused by A. cantonensis infections. The mechanism steroids act on eosinophilic meningitis remains unclear. In this mouse experiments, expressions of 14-3-3 isoform ${\beta}$ and ${\gamma}$ proteins significantly increased in the CSF 2-3 weeks after the infection, but not increasedin the dexamethasone-treated group. Expression of 14-3-3 ${\beta}$, ${\gamma}$, ${\varepsilon}$, and ${\theta}$ isoforms increased in brain meninges over the 3-week period after infection and decreased due to dexamethasone treatment. In conclusion, administration of dexamethasone in mice with eosinophilic meningitis decreased expressions of 14-3-3 isoform proteins in the CSF and in brain meninges.

Brain plasticity and ginseng

  • Myoung-Sook Shin;YoungJoo Lee;Ik-Hyun Cho;Hyun-Jeong Yang
    • Journal of Ginseng Research
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    • v.48 no.3
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    • pp.286-297
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    • 2024
  • Brain plasticity refers to the brain's ability to modify its structure, accompanied by its functional changes. It is influenced by learning, experiences, and dietary factors, even in later life. Accumulated researches have indicated that ginseng may protect the brain and enhance its function in pathological conditions. There is a compelling need for a more comprehensive understanding of ginseng's role in the physiological condition because many individuals without specific diseases seek to improve their health by incorporating ginseng into their routines. This review aims to deepen our understanding of how ginseng affects brain plasticity of people undergoing normal aging process. We provided a summary of studies that reported the impact of ginseng on brain plasticity and related factors in human clinical studies. Furthermore, we explored researches focused on the molecular mechanisms underpinning the influence of ginseng on brain plasticity and factors contributing to brain plasticity. Evidences indicate that ginseng has the potential to enhance brain plasticity in the context of normal aging by mediating both central and peripheral systems, thereby expecting to improve age-related declines in brain function. Moreover, given modern western diet can damage neuroplasticity in the long term, ginseng can be a beneficial supplement for better brain health.

Neuroprotective Effects of Protein Tyrosine Phosphatase 1B Inhibition against ER Stress-Induced Toxicity

  • Jeon, Yu-Mi;Lee, Shinrye;Kim, Seyeon;Kwon, Younghwi;Kim, Kiyoung;Chung, Chang Geon;Lee, Seongsoo;Lee, Sung Bae;Kim, Hyung-Jun
    • Molecules and Cells
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    • v.40 no.4
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    • pp.280-290
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    • 2017
  • Several lines of evidence suggest that endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Protein tyrosine phosphatase 1B (PTP1B) is known to regulate the ER stress signaling pathway, but its role in neuronal systems in terms of ER stress remains largely unknown. Here, we showed that rotenone-induced toxicity in human neuroblastoma cell lines and mouse primary cortical neurons was ameliorated by PTP1B inhibition. Moreover, the increase in the level of ER stress markers ($eIF2{\alpha}$ phosphorylation and PERK phosphorylation) induced by rotenone treatment was obviously suppressed by concomitant PTP1B inhibition. However, the rotenone-induced production of reactive oxygen species (ROS) was not affected by PTP1B inhibition, suggesting that the neuroprotective effect of the PTP1B inhibitor is not associated with ROS production. Moreover, we found that MG132-induced toxicity involving proteasome inhibition was also ameliorated by PTP1B inhibition in a human neuroblastoma cell line and mouse primary cortical neurons. Consistently, downregulation of the PTP1B homologue gene in Drosophila mitigated rotenone- and MG132-induced toxicity. Taken together, these findings indicate that PTP1B inhibition may represent a novel therapeutic approach for ER stress-mediated neurodegenerative diseases.

A Study on the correlation between Sung-Jung' concept of Sasang Constitutional Medicine and Brain (사상의학(四象醫學)에 나타난 성정(性情)의 개념과 뇌(腦)와의 상관성에 관한 고찰)

  • Kim, Jong-Weon;Seul, Yu-Kyung
    • Journal of Sasang Constitutional Medicine
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    • v.12 no.2
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    • pp.17-33
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    • 2000
  • Purpose of this study is to investigate the correlation between Sung-Jung' concept of Sasang Constitutional Medicine and Brain. So, After studying the meaning of Sung-Jung' concept of Sasang Constitutional Medicine, I made a comparative study through the structure, function, development of Brain. The conclusions were as follows. 1. Human's brain acts a rational, control his actions. and It manage human body's physiology and pathology. and It perceive his surroundings, express his emotion through comprehension, synthesis, judgement about information from various fields. and It's abnormality bring about a spiritual, bodily injury. Therefore, human's brain have many correlation with Sung-Jung' concept of Sasang Constitutional Medicine. 2. Neocortex' function have many correlation with Sung' concept of Hearing-Sight-Smell-Taste (聽視嗅味=sensation=a highly mental capacity) through Ear-Eye-Nose-Mouse(耳目鼻?). 3. Limbic-system'function have many correlation with Jung' concept of Sorrow-Anger-Pleasure-Joy(哀怒喜榮=emotion) through Lung-Spleen-Liver-Kidney(肺脾肝腎) 4. Brain-stem' function have many correlation with vitalistic concept through Qui of Sorrow - Anger - Pleasure - Joy(哀怒喜樂之氣)' rise and fall. 5. Relation of emotions and diseases through Limbic system and Autonomic nervous system have many correlation with relation of Sung-Jung and diseases of Sasang Constitutional Medicine 6. Left-hemisphere' function that has superior power of verbal, analysis, logicality, consideration have many correlation with tendency of Soeumin and Taeumin. and Right-hemisphere' function that has superior power of emotion, non-verbal, imagination, spatial perception have many correlation with tendency of Soyangin and Taeyangin.

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Implications of Circadian Rhythm in Dopamine and Mood Regulation

  • Kim, Jeongah;Jang, Sangwon;Choe, Han Kyoung;Chung, Sooyoung;Son, Gi Hoon;Kim, Kyungjin
    • 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.

Effect of LI4-LI11 Electro-acupuncture on Regional Cerebral Blood Flow in Healthy Human - Evaluated by $^{99m}Tc-ECD$ Brain SPECT - (합곡-곡지 전침치료가 정상인의 뇌혈류에 미치는 영향 - Brain SPECT와 SPM을 이용하여 -)

  • Ryu Jong-Man;Kim Young-Suk;Park Sung-Uk;Jung Woo-Sang;Ko Chang-Nam;Cho Ki-Ho;Bae Hyung-Sup;Kim Deok-Yoon;Moon Sang-Kwan
    • The Journal of Korean Medicine
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    • v.27 no.2 s.66
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    • pp.36-43
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    • 2006
  • Objectives : Acupuncture has been widely applied to rehabilitation after stroke by Oriental medical doctors in Korea. It has been reported that acupuncture increased cerebral blood supply and stimulated the functional activity of brain nerve cells. In addition, a correlation between activation of specific areas of brain cortices and corresponding acupuncture stimulation at the therapeutic points had been well illustrated. rill now, however, there were few studies which evaluated a correlation between activation of specific areas of brain and frequently-used acupuncture therapy for stroke, such as LI4-LI11 electro-acupuncture (EA) for paresis after stroke. This study was undertaken to evaluate the effect of LI4-LI11 EA on regional cerebral blood flow (rCBF) in normal volunteers using Single Photon Emission Computed Tomography (SPECT). Methods : In the resting state, $^{99m}Tc-ECD$ brain SPECT scans were performed on 10 normal volunteers (8 males, 2 females, mean age $25.6{\pm}2.3$years; age range from 24 to 31 years). 7 days after the resting examination, 15 minutes of electro-acupuncture were applied at LI 4 and LI 11 on the right side of the subjects. Immediately after LI4-LI11 EA, the second SPECT images were obtained in the same manner as the resting state. Significant increases and decreases of regional cerebral blood flow after LI4-LI11 EA were estimated by comparing their SPECT images with those of the resting state using paired t statistics at every voxel, which were analyzed by Statistical parametric mapping with a threshold of p=0.001, uncorrected (extent threshold: k=100 voxels). Results : EA applied at right LI4-LI11 increased rCBF in right frontopolar area (Brodmann area 10) and left middle frontal area (Brodmann area 46). Interestingly, all the areas showing increased rCBF corresponded to the territories of both anterior cerebral arteries. However, LI4-11 EA decreased rCBF in the left occipital lobe (peristriate area, Brodmann area 19). Conclusions : The results demonstrated a correlation between LI4-11 EA and rCBF increase in the frontal lobes. It is also suggested that there may be a correlation between LI meridian and the territory of the anterior cerebral arterties.

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Newly Developed Weakness of Lower Extremities Despite Improved Brain Metastasis of Lung Cancer after Radiotherapy

  • Yang, Jae Hyun;Jang, Young Joo;Ahn, Se Jin;Kim, Hye-Ryoun;Kim, Cheol Hyeon;Koh, Jae Soo;Choe, Du Hwan;Lee, Jae Cheol
    • Tuberculosis and Respiratory Diseases
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    • v.67 no.6
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    • pp.574-576
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    • 2009
  • An intramedullary spinal cord metastasis (ISCM) rarely develops in systemic cancer but is indicative of a poor prognosis. A 56-year-old man was admitted due to weakness of the lower extremities. He had received radiotherapy 3 months prior for a brain metastasis that had developed 1 year after achieving a complete response from chemotherapy for extended stage small cell lung cancer. Although the brain lesion had improved partially, ISCM from the cervical to lumbar-sacral spinal cords, which was accompanied by a leptomeningeal dissemination, was diagnosed based on magnetic resonance imaging of the spine and cerebrospinal fluid cytology. Finally, he died of sudden cardiac arrest during treatment. This is the first case of ISCM involving the whole spinal segments. Physicians should be aware of the subsequent development of ISCM in lung cancer patients with a previously known brain metastasis who present with new neurological symptoms.

The Effect of Systemic Hypertension on the Pediatric Brain (중추신경계에 미치는 소아 고혈압의 영향)

  • Hur, Yun-Jung
    • Childhood Kidney Diseases
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    • v.15 no.1
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    • pp.22-28
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    • 2011
  • Hypertension is one of the most common chronic diseases in childhood and adolescence. Untreated hypertension adversely affects many organs including heart, brain, kidney and peripheral arteries. We reviewed the complication of central nervous system caused by pediatric hypertension. Cerebral blood flows are maintained constantly in response to changes in blood pressure by cerebral autoregulation. Severe hypertension which destructs cerebral autoregulation results in acute hypertensive encephalopathy syndrome, ischemic or hemorrhagic stroke. Chronic pediatric hypertension induces learning disability and cognitive defect which are subclinical symptom prior to brain damage caused by severe hypertension. We should consider the effect of hypertension on pediatric brain because appropriate antihypertensive drugs could prevent these complications.