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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2021.1
- 수록면
- 232 - 243 (12page)
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Mutations in the Leucine-rich repeat kinase 2 (LRRK2) gene are the most prevalent cause of familial Parkinson’s disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells. In contrast, treatment of SH-SY5Y dopaminergic neuronal cells with PD-causing chemicals increased ciliogenesis. Because these reports were somewhat contradictory, we tested the effect of LRRK2 kinase activity on ciliogenesis in neurons. In SH-SY5Y cells, LRRK2 inhibitor treatment slightly increased ciliogenesis, but serum starvation showed no increase. In rat primary neurons, LRRK2 inhibitor treatment repeatedly showed no significant change. Little difference was observed between primary cortical neurons prepared from wild-type (WT) and G2019S+/- mice. However, a significant increase in ciliogenesis was observed in G2019S+/- compared to WT human fibroblasts, and this pattern was maintained in neural stem cells (NSCs) differentiated from the induced pluripotent stem cells (iPSCs) prepared from the same WT/G2019S fibroblast pair. NSCs differentiated from G2019S and its gene-corrected WT counterpart iPSCs were also used to test ciliogenesis in an isogenic background. The results showed no significant difference between WT and G2019S regardless of kinase inhibitor treatment and B27-deprivation-mimicking serum starvation. These results suggest that LRRK2 kinase activity may be not a direct regulator of ciliogenesis and ciliogenesis varies depending upon the cell type or genetic background.
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참고문헌 (39)
참고문헌 신청
설원기 / 2010 / Biochemical and molecular features of LRRK2 and its pathophysiological roles in Parkinson’s disease / BMB Reports 43(4):233~244
Cookson MR / 2017 / Mechanisms of mutant LRRK2 neurodegeneration / Adv Neurobiol 14:227~239
Monfrini E / 2017 / Leucine-rich repeat kinase(LRRK2)genetics and Parkinson's disease / Adv Neurobiol 14:3~30
West AB / 2005 / Parkinson's diseaseassociated mutations in leucine-rich repeat kinase 2 augment kinase activity / Proc Natl Acad Sci U S A 102:16842~16847
Lesage S / 2006 / LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs / N Engl J Med 354:422~423
Cookson MR / 2017 / Mechanisms of mutant LRRK2 neurodegeneration / Adv Neurobiol 14:227~239
Monfrini E / 2017 / Leucine-rich repeat kinase(LRRK2)genetics and Parkinson's disease / Adv Neurobiol 14:3~30
West AB / 2005 / Parkinson's diseaseassociated mutations in leucine-rich repeat kinase 2 augment kinase activity / Proc Natl Acad Sci U S A 102:16842~16847
Lesage S / 2006 / LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs / N Engl J Med 354:422~423
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