• 제목/요약/키워드: pathogenesis mechanism

검색결과 321건 처리시간 0.028초

Role of post-translational modifications on the alpha-synuclein aggregation-related pathogenesis of Parkinson's disease

  • Yoo, Hajung;Lee, Jeongmin;Kim, Bokwang;Moon, Heechang;Jeong, Huisu;Lee, Kyungmi;Song, Woo Jeung;Hur, Junho K.;Oh, Yohan
    • BMB Reports
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    • 제55권7호
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    • pp.323-335
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    • 2022
  • Together with neuronal loss, the existence of insoluble inclusions of alpha-synuclein (α-syn) in the brain is widely accepted as a hallmark of synucleinopathies including Parkinson's disease (PD), multiple system atrophy, and dementia with Lewy body. Because the α-syn aggregates are deeply involved in the pathogenesis, there have been many attempts to demonstrate the mechanism of the aggregation and its potential causative factors including post-translational modifications (PTMs). Although no concrete conclusions have been made based on the previous study results, growing evidence suggests that modifications such as phosphorylation and ubiquitination can alter α-syn characteristics to have certain effects on the aggregation process in PD; either facilitating or inhibiting fibrillization. In the present work, we reviewed studies showing the significant impacts of PTMs on α-syn aggregation. Furthermore, the PTMs modulating α-syn aggregation-induced cell death have been discussed.

Emerging role of bystander T cell activation in autoimmune diseases

  • Shim, Chae-Hyeon;Cho, Sookyung;Shin, Young-Mi;Choi, Je-Min
    • BMB Reports
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    • 제55권2호
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    • pp.57-64
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    • 2022
  • Autoimmune disease is known to be caused by unregulated self-antigen-specific T cells, causing tissue damage. Although antigen specificity is an important mechanism of the adaptive immune system, antigen non-related T cells have been found in the inflamed tissues in various conditions. Bystander T cell activation refers to the activation of T cells without antigen recognition. During an immune response to a pathogen, bystander activation of self-reactive T cells via inflammatory mediators such as cytokines can trigger autoimmune diseases. Other antigen-specific T cells can also be bystander-activated to induce innate immune response resulting in autoimmune disease pathogenesis along with self-antigen-specific T cells. In this review, we summarize previous studies investigating bystander activation of various T cell types (NKT, γδ T cells, MAIT cells, conventional CD4+, and CD8+ T cells) and discuss the role of innate-like T cell response in autoimmune diseases. In addition, we also review previous findings of bystander T cell function in infection and cancer. A better understanding of bystander-activated T cells versus antigen-stimulated T cells provides a novel insight to control autoimmune disease pathogenesis.

Priming of Defense-Related Genes Confers Root-Colonizing Bacilli-Elicited Induced Systemic Resistance in Pepper

  • Yang, Jung-Wook;Yu, Seung-Hun;Ryu, Choong-Min
    • The Plant Pathology Journal
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    • 제25권4호
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    • pp.389-399
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    • 2009
  • A group of beneficial plant bacteria has been shown to increase crop growth referring to as plant growth-promoting rhizobacteria (PGPR). PGPR can decrease plant disease directly, through the production of antagonistic compounds, and indirectly, through the elicitation of a plant defense response termed induced systemic resistance (ISR). While the mechanism of PGPR-elicited ISR has been studied extensively in the model plant Arabidopsis, it is less well characterized in crop plants such as pepper. In an effort to better understand the mechanism of ISR in crop plants, we investigated the induction of ISR by Bacillus cereus strain BS107 against Xanthomonas axonopodis pv. vesicatoria in pepper leaves. We focused on the priming effect of B. cereus strain BS107 on plant defense genes as an ISR mechanism. Of ten known pepper defense genes that were previously reported to be involved in pathogen defense signaling, the expression of Capsicum annum pathogenesis-protein 4 and CaPR1 was systemically primed by the application of strain BS107 onto pepper roots confirming by quantitative-reverse transcriptase PCR. Our results provide novel genetic evidence of the priming effect of a rhizobacterium on the expression of pepper defense genes involved in ISR.

태아모체간 계면에서의 면역학적 측면 (Immunologic Aspects at the Feto-Maternal Interface)

  • 정인배
    • 한국발생생물학회지:발생과생식
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    • 제5권2호
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    • pp.93-100
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    • 2001
  • 태아가 모체의 면역 거부 반응으로부터 회피될 수 있는 기전에 관한 연구는 반세기를 지내왔지만 아직까지 규명되지 못하고 있다. 태아모체간 계면에서의 면역학적 기전이상은 자연 유산 및 습관성 유산, 태아발육제한, 임신성 고혈압 질환, 보조 생식술 후 착상실패, 태아 사망 등 각종 임신 합병증들의 병인으로 작용하므로 이 기전 규명은 매우 중요하다. 본 종설에서는 현재까지 이 면역학적 기전에 관해 밝혀진 내용들이 그 중요성의 정도순으로 기술되었다. 그 기전 이해에 관해서는 1) 융모외 세포영양모세포(extravillous cytotrophoblasts)가 표현하는 인백혈구 항원(HLA-C, E, G)과 자연살세포 수용체(NK cell receptor)들과 상호 관계가 그 핵심으로 2) 면역 조정(immunomodulation)과 3) 선천면역(innate immunity)이 주된 기전이고 4) 보체(complement) 등 인백혈구 항원계(HLA system)이외의 인자들이 관여함 등으로 요약될 수 있고 이러한 무수한 기전들의 종합적인 면역 조정 결과가 해당 임신의 예후를 결정하게 될 것이다. 향후, 각 기전에 대한 연구들, 특히 융모외 세포영양모세포(extravillous cytotrophoblasts)의 인백혈구 항원(HLA antigens)과 그 수용체(receptor)들의 조절기전, 사이토카인(cytokine), 보체(complement) 등의 역할에 관한 더욱 많은 연구가 진척되어야할 것이다.

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항정신병 약물과 혈당조절이상 (Antipsychotics and Abnormality in Glucose Regulation)

  • 황재승;김현;권영준;정희연
    • 생물정신의학
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    • 제10권2호
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    • pp.107-115
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    • 2003
  • Objective:The purpose of this study was to know about the mechanism of pathogenesis of type 2 diabetes mellitus by using of blood glucose, glucoregulatory factor, insulin resistance in schizophrenic patients receiving antipsychotics. Method:Modified oral glucose tolerance tests were performed in 20 schizophrenic patients receiving haloperidol, risperidone and olanzapine. Insulin, glucagon, C-peptide and cortisol were measured in 0, 15, 45, 75 minutes after glucose loading, and insulin resistance was calculated by HOMA(homeostasis model assessment) method. Result:Olanzapine-treated patients had significant glucose elevation 45 minutes after glucose challenge. Also modest increases in HOMA IR values were detected in patients treated with olanzapine. Conclusion:Olanzapine treatment of non-diabetic patients with schizophrenia can be associated with type 2 diabetes mellitus through the elevation of glucose and insulin resistance. Elevated insulin resistance may be a causative mechanism of type 2 diabetes mellitus in patients receiving olanzapine.

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Significance of Hemodynamic Effects on the Generation of Atherosclerosis

  • Suh Sang-Ho;Roh Hyung-Woon;Kim Dong-Joo;Kwon Hyuck-Moon;Lee Byoung-Kwon
    • Journal of Mechanical Science and Technology
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    • 제19권3호
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    • pp.836-845
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    • 2005
  • Atherosclerosis, which is a degenerative vascular disease, is believed to occur in the blood vessels due to deposition of cholesterol or low density lipoprotein (LDL). Atherosclerotic lumen narrowing causes reduction of blood flow due to hemodynamic features. Several hypothetical theories related to the hemodynamic effects have been reported : high shear stress theory, low shear stress theory, high shear stress gradient theory, flow separation and turbulence theory, and high pressure theory. However, no one theory clearly explains, the causes of atherosclerosis. The objective of the present study was to investigate the mechanism of the generation of atherosclerosis. In the study, the database of Korean carotid and coronary arteries for geometrical and hemodynamic clinical data was established. The atherosclerotic sites were predicted by the computer simulations. The results of the computer simulation were compared with the in vivo experimental results, and then the pathogenesis of atherosclerosis by using the clinical data and several hypothetical theories were investigated. From the investigation, it was concluded carefully that the mechanism of the generation of atherosclerosis was related to the hemodynamic effects such as flow separation and oscillatory wall shear stress on the vessel walls.

MRONJ 예방과 치료를 위한 최신지견 (Contemporary Concept for Prevention and treatment of MRONJ (Medication Related Osteonecrosis of Jaw))

  • 박정현;김선종
    • 대한치과의사협회지
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    • 제54권4호
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    • pp.274-283
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    • 2016
  • Bisphosphonates are widely used mainly for the treatment of osteoporosis and bone metastasis of malignancy. Since the first report of MRONJ, there have been many studies associated, however the pathogenesis of MRONJ is not yet clear. Medication-related osteonecrosis of the jaws (MRONJ) is a serious complication associated with long-term medication therapy. It is characterized by exposed necrotic bonein the jaw, which has persisted for more than 8weeks despite continuous treatment by dentist. The mechanism of development of MRONJ is still unclear and there is no definitive standard treatment for MRONJ. The purpose of this study is to investigate the jaw bone destruction mechanism of accumulated bisphosphonates, so that we can develop therapeutic method to repair the defect and stop the destruction process. The authors performed simultaneous application of PRF(Platelet rich fibrin) and BMP-2(Bone morphogenetic protein-2) to stimulate not only soft tissue healing but also osseous regeneration. Our case series demonstrate that simultaneous application of platelet rich fibrin and bone morphogenetic protein-2 can be a treatment of choice for MRONJ.

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조현병(調鉉病) : 뇌 연결성의 장애 (Attunement Disorder : A Disorder of Brain Connectivity)

  • 김기원;박경민;장혜련;이유상;박선철
    • 생물정신의학
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    • 제20권4호
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    • pp.136-143
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    • 2013
  • Objectives We reviewed cellular and synaptic dysconnectivity, disturbances in micro- and macro- circuitries, and neurodevelopmentally-derived disruptions of neural connectivity in the pathogenesis of schizophrenia. Method We reviewed the selected articles about disturbances in neural circuits which had been proposed as a pathogenetic mechanism of schizophrenia. Results The literature review reveals that schizophrenia may be a disease related to disturbance in neurodevelopmental mechanism, shown as 'a misconnection syndrome of neural circuit or neural network'. In descriptive psychopathological view, definition of a disorder of brain connectivity has limitation to explain other aspects of schizophrenia including deterministic strictness in thought process. Conclusion Schizophrenia is considered as a disorder of brain connectivity as well as a neurodevelopmental disorder related with genetic and environmental factors. We could make a suggestion that "JoHyeonByung (attunement disorder)" denotes the disturbances of psychic fine-tuning which correspond to the neural correlates of brain dysconnectivity metaphorically.

Neuroimmunological Mechanism of Pruritus in Atopic Dermatitis Focused on the Role of Serotonin

  • Kim, Kwangmi
    • Biomolecules & Therapeutics
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    • 제20권6호
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    • pp.506-512
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    • 2012
  • Although pruritus is the critical symptom of atopic dermatitis that profoundly affect the patients' quality of life, controlling and management of prurirtus still remains as unmet needs mainly due to the distinctive multifactorial pathogenesis of pruritus in atopic dermatitis. Based on the distinct feature of atopic dermatitis that psychological state of patients substantially influence on the intensity of pruritus, various psychotropic drugs have been used in clinic to relieve pruritus of atopic dermatitis patients. Only several psychotropic drugs were reported to show real antipruritic effects in atopic dermatitis patients including naltrexone, doxepin, trimipramine, bupropion, tandospirone, paroxetine and fluvoxamine. However, the precise mechanisms of antipruritic effect of these psychotropic drugs are still unclear. In human skin, serotonin receptors and serotonin transporter protein are expressed on skin cells such as keratinocytes, melanocytes, dermal fibroblasts, mast cells, T cells, natural killer cells, langerhans cells, and sensory nerve endings. It is noteworthy that serotonergic drugs, as well as serotonin itself, showed immune-modulating effect. Fenfluramine, fluoxetine and 2, 5-dimethoxy-4-iodoamphetamine significantly decreased lymphocyte proliferation. It is still questionable whether these serotonergic drugs exert the immunosuppressive effects via serotonin receptor or serotonin transporter. All these clinical and experimental reports suggest the possibility that antipruritic effects of selective serotonin reuptake inhibitors in atopic dermatitis patients might be at least partly due to their suppressive effect on T cells. Further studies should be conducted to elucidate the precise mechanism of neuroimmunological interaction in pruritus of atopic dermatitis.

The Inhibitory Effect and Mechanism of Luteolin 7-Glucoside on Rat Aortic Vascular Smooth Muscle Cell Proliferation

  • Kim, Tack-Joong;Kim, Jin-Ho;Jin, Yong-Ri;Yun, Yeo-Pyo
    • Archives of Pharmacal Research
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    • 제29권1호
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    • pp.67-72
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    • 2006
  • The abnormal proliferation of aortic vascular smooth muscle cells (VSMCs) plays a central role in the pathogenesis of atherosclerosis and restenosis after angioplasty and possibly also in the development of hypertension. The present study was designed to examine the inhibitory effects and the mechanism of luteolin 7-glucoside (L7G) on the platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs. L7G significantly inhibited the PDGF-BB-induced proliferation and the DNA synthesis of the VSMCs in a concentration-dependent manner. Pre-incubation of the VSMCs with L7G significantly inhibited the PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2), Akt and the phospholipase C $(PLC)-{\gamma}1$ activation. However, L7G had almost no affect on the phosphorylation of $PDGF-{\beta}$ receptor tyrosine kinase, which was induced by PDGF-BB. These results suggest that L7G inhibits the PDGF-BB-induced proliferation of VSMCs via the blocking of $(PLC)-{\gamma}1$, Akt, and ERK1/2 phosphorylation.