ADP로 활성화된 microglia의 actin dynamics를 조절하는 LRRK2 작용 연구

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dc.contributor.authorByun, Ji Won-
dc.description학위논문(석사)--아주대학교 일반대학원 :의생명학과,2014. 2-
dc.description.tableofcontentsABSTRACT ⅰ TABLE OF CONTENTS ⅲ LIST OF FIGURES ⅴ Ⅰ. INTRODUCTION 1 A. Parkinsons disease and related genes 1 B. LRRK2 regulates actin dynamics and microglial motility 1 C. Focal adhesion kinase (FAK) as a master molecule that regulates adhesion and movement of cells 2 D. Specific aims 4 Ⅱ. MATERIAL AND METHODS 5 A. Transgenic mice 5 B. Cell culture 5 C. Time-lapse microscopy 6 D. Immunofluorescence staining 6 E. siRNA transfection 6 F. Immunoprecipitation (IP) assay 7 G. Western blot 7 H. In vivo stab wound assay 8 I. Immunohistochemistry 8 Ⅲ. RESULTS 10 Ⅳ. DISCUSSION 24 Ⅴ. CONCLUSION 26 REFERENCES 27 국문요약 31-
dc.publisherThe Graduate School, Ajou University-
dc.rights아주대학교 논문은 저작권에 의해 보호받습니다.-
dc.titleADP로 활성화된 microglia의 actin dynamics를 조절하는 LRRK2 작용 연구-
dc.title.alternativeJi-Won Byun-
dc.contributor.affiliation아주대학교 일반대학원-
dc.contributor.alternativeNameJi-Won Byun-
dc.contributor.department일반대학원 의생명과학과- 2-
dc.description.alternativeAbstractParkinson’s disease (PD) is a neurodegenerative disease caused by dopaminergic neuronal death in the substantia nigra. Microglia are brain macrophages that continuously survey the microenvironment of the brain to find out and repair brain damage. Although PD associated genes are expressed in microglia, their roles in these cells are largely unknown. The present study revealed that LRRK2, a PD-associated gene, regulates the migration of microglia. LRRK2 was located in ruffles, an actin rich structure of moving cells, when ADP induced microglial movement. In immunoprecipation assay, LRRK2 interacted with focal adhesion kinase (FAK), a protein that regulates the adhesion and migration of cells. LRRK2 and FAK were co-localized with ruffles when microglia actively moved. The overexpression of LRRK2 reduced the phosphorylated FAK levels compared with that of the mock, which suggests that LRRK2 inhibits FAK activation. LRRK2 G2019S, a pathologic LRRK2 mutant, more significantly inhibited the FAK activation and the movement of microglia than non-transgenic LRRK2 did. Furthermore, microglial migration defects were also observed in stab-wounded LRRK2 G2019S TG mice brain. Taken together, these results suggest that LRRK2 suppresses microglial movement by inhibiting FAK activation. Importantly, mutations of LRRK2, such as G2019S, could increase the risk of PD development, since microglia could not properly respond to and repair brain damage.-
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Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
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