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파킨슨병 유전자 DJ-1에 의한 성상세포 기능 조절 연구
- Alternative Title
- Regulation of Astrocyte Functions by a Parkinson's Disease Gene, DJ-1
- Author(s)
- 최동주
- Alternative Author(s)
- Dong-Joo Choi
- Advisor
- 조은혜
- Department
- 일반대학원 의생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2016--8
- Language
- eng
- Alternative Abstract
- Parkinson’s disease (PD) is a neurodegenerative motor disease, accompanied by loss of dopaminergic neurons in the substantia nigra. PD genes have been studied to reveal molecular mechanisms of onset and progression of PD. In this study, I investigated the effect of a PD gene, DJ-1, on astrocyte function since astrocytes as the most abundant cells in the brain play diverse roles for well-being and function of the brain. In the first part, I investigated behavior of astrocytes in ATP-injured striatum. In response to injury, DJ-1 KO astrocytes did not undergo proper gliosis: less increase in expression of GFAP, nestin, and GDNF, and less hypertrophic. In addition, damage areas in DJ-1 KO brain were slowly recovered with astrocytes and TH-positive neurites compared with WT brain. As an underlying mechanism, I found that DJ-1 deficiency attenuateded activation of STAT3, a transcription factor that regulates expression of GFAP and nestin. In the second part of the study, I investigated anti-inflammatory roles of astrocytes regulated by DJ-1. DJ-1 deficient astrocytes less efficiently reduced microglial expression of proinflammatory mediators such as iNOS and TNF-. DJ-1 KO astrocytes compared with WT astrocytes less produced anti-inflammatory prostaglandin, prostaglandin D2 (PGD2), through attenuated expression of lipocalin-type PGD2 synthase (L-PGDS). DJ-1 regulates protein stability of Sox9, a transcription factor that regulates L-PGDS expression. Thus, in the absence of DJ-1, Sox9 ubiquitination was increased and the protein was degraded. Taken together, these results indicate that DJ-1 regulated numerous functions of astrocytes. Therefore, DJ-1 deficiency may affect onset and/or progression of PD due to defects in astrocyte function in intact and injured brain.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Biomedical Sciences > 4. Theses(Ph.D)
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