지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.6
- 수록면
- 177 - 184 (8page)
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초록· 키워드
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Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson’s disease (PD). LRRK2 contains a functional kinase and GTPase domains. A pathogenic G2019S mutation that is the most prevalent among the LRRK2 mutations and is also found in sporadic cases, increases its kinase activity. Therefore, identification of LRRK2 kinase substrates and the development of kinase inhibitors are under intensive investigation to find PD therapeutics. Several recent studies have suggested members of Rab proteins, a branch of the GTPase superfamily, as LRRK2 kinase substrates. Rab proteins are key regulators of cellular vesicle trafficking. Among more than 60 members of human Rab proteins, Rab3, Rab5, Rab8, Rab10, Rab12, Rab29, Rab35, and Rab43 have been identified as LRRK2 kinase substrates. However, most studies have used human embryonic kidney (HEK) 293T cells overexpressing LRRK2/Rab proteins or murine embryonic fibroblast (MEF) cells which are not relevant to PD, rather than neuronal cells. In this study, we tested whether Rab proteins are phosphorylated by LRRK2 in astroglia in addition to neurons. Among the various Rab substrates, we tested phosphorylation of Rab10, because of the commercial availability and credibility of the phospho-Rab10 (pRab10) antibody, in combination with a specific LRRK2 kinase inhibitor. Based on the results of specific LRRK2 kinase inhibitor treatment, we concluded that LRRK2 phosphorylates Rab10 in the tested brain cells such as primary neurons, astrocytes and BV2 microglial cells.
목차
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
참고문헌 (37)
참고문헌 신청
Arranz AM / 2015 / LRRK2 functions in synaptic vesicle endocytosis through a kinase-dependent mechanism / J Cell Sci 128:541~552
Atashrazm F / 2019 / LRRK2-mediated Rab10 phosphorylation in immune cells from Parkinson's disease patients / Mov Disord 34:406~415
Belin AC / 2008 / Parkinson's disease: a genetic perspective / Febs J 275:1377~1383
Christensen KV / 2018 / LRRK2 exonic variants associated with Parkinson's disease augment phosphorylation levels for LRRK2-Ser1292 and Rab10-Thr73 / BioRxiv
Di Maio R / 2018 / LRRK2 activation in idiopathic Parkinson's disease / Sci Transl Med 10:451
Atashrazm F / 2019 / LRRK2-mediated Rab10 phosphorylation in immune cells from Parkinson's disease patients / Mov Disord 34:406~415
Belin AC / 2008 / Parkinson's disease: a genetic perspective / Febs J 275:1377~1383
Christensen KV / 2018 / LRRK2 exonic variants associated with Parkinson's disease augment phosphorylation levels for LRRK2-Ser1292 and Rab10-Thr73 / BioRxiv
Di Maio R / 2018 / LRRK2 activation in idiopathic Parkinson's disease / Sci Transl Med 10:451
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UCI(KEPA) : I410-ECN-0101-2019-510-000875067