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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
- 2020.1
- 수록면
- 821 - 830 (10page)
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Altered dendritic morphology is frequently observed in various neurological disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the cellular and molecular basis underlying these pathogenic dendritic abnormalities remains largely unclear. In this study, we investigated dendritic morphological defects caused by dipeptide repeat protein (DPR) toxicity associated with G4C2 expansion mutation of C9orf72 (the leading genetic cause of ALS and FTD) in Drosophila neurons and characterized the underlying pathogenic mechanisms. Among the five DPRs produced by repeat-associated non-ATG translation of G4C2 repeats, we found that arginine-rich DPRs (PR and GR) led to the most significant reduction in dendritic branches and plasma membrane (PM) supply in Class IV dendritic arborization (C4 da) neurons. Furthermore, expression of PR and GR reduced the number of Golgi outposts (GOPs) in dendrites. In Drosophila brains, expression of PR, but not GR, led to a significant reduction in the mRNA level of CrebA, a transcription factor regulating the formation of GOPs. Overexpressing CrebA in PR-expressing C4 da neurons mitigated PM supply defects and restored the number of GOPs, but the number of dendritic branches remained unchanged, suggesting that other molecules besides CrebA may be involved in dendritic branching. Taken together, our results provide valuable insight into the understanding of dendritic pathology associated with C9-ALS/FTD.
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참고문헌 (56)
참고문헌 신청
Boivin, M. / 2020 / Reduced autophagy upon C9ORF72loss synergizes with dipeptide repeat protein toxicity in G4C2 repeat expansion disorders / EMBO J 39:e100574
Burk, K. / 2019 / Disrupted neuronal trafficking in amyotrophic lateral sclerosis / Acta Neuropathol 137:859~877
Caracci, M. O. / 2019 / Golgi complex dynamics and its implication in prevalent neurological disorders / Front. Cell Dev. Biol 7:75
Chung, C. G. / 2017 / Golgi outpost synthesis impaired by toxic polyglutamine proteins contributes to dendritic pathology in neurons / Cell Rep 20:356~369
Clayton, E. L. / 2018 / Frontotemporal dementia causative CHMP2B impairs neuronal endolysosomal traffic-rescue by TMEM106B knockdown / Brain 141:3428~3442
Burk, K. / 2019 / Disrupted neuronal trafficking in amyotrophic lateral sclerosis / Acta Neuropathol 137:859~877
Caracci, M. O. / 2019 / Golgi complex dynamics and its implication in prevalent neurological disorders / Front. Cell Dev. Biol 7:75
Chung, C. G. / 2017 / Golgi outpost synthesis impaired by toxic polyglutamine proteins contributes to dendritic pathology in neurons / Cell Rep 20:356~369
Clayton, E. L. / 2018 / Frontotemporal dementia causative CHMP2B impairs neuronal endolysosomal traffic-rescue by TMEM106B knockdown / Brain 141:3428~3442
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