基本情報
研究キーワード
10経歴
8-
2013年 - 現在
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2009年 - 2013年
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2005年 - 2009年
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2000年 - 2002年
学歴
1-
1982年 - 1988年
委員歴
6-
2021年 - 現在
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2021年 - 現在
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2014年 - 現在
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2013年 - 現在
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2011年 - 現在
受賞
2論文
146-
Neuromuscular disorders : NMD 31(9) 839-846 2021年9月To clarify the influence of coronavirus disease-19 (COVID-19) on the care of muscular dystrophy patients, we performed a questionnaire survey that was posted on the internet on May 11, 2020. By the end of July 2020, 542 responses had been collected. Approximately 30% of patients postponed regular consultations, and one-quarter of patients who received consultation more than once a month used telephone consultations. Two of 84 patients with Duchenne muscular dystrophy had reduced their steroid doses. A shortage of ventilator accessories and infection protection equipment occurred following the onset of COVID-19, and this shortage had a serious impact on medical care and infection prevention measures. Reductions in rehabilitation and other services, and avoidance of outings, led to a decrease in exercise and an increase in caregiver burden. Inpatients were restricted from going out and visiting family members. More than 20% of patients reported physical or mental complaints; however, few required treatment. COVID-19 has seriously affected the activities and quality of life of patients with muscular dystrophy. We will continue this survey and analyze the longitudinal changes.
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Science advances 7(3) 2021年1月Fragile X-related tremor/ataxia syndrome (FXTAS) is a neurodegenerative disease caused by CGG triplet repeat expansions in FMR1, which elicit repeat-associated non-AUG (RAN) translation and produce the toxic protein FMRpolyG. We show that FMRpolyG interacts with pathogenic CGG repeat-derived RNA G-quadruplexes (CGG-G4RNA), propagates cell to cell, and induces neuronal dysfunction. The FMRpolyG polyglycine domain has a prion-like property, preferentially binding to CGG-G4RNA. Treatment with 5-aminolevulinic acid, which is metabolized to protoporphyrin IX, inhibited RAN translation of FMRpolyG and CGG-G4RNA-induced FMRpolyG aggregation, ameliorating aberrant synaptic plasticity and behavior in FXTAS model mice. Thus, we present a novel therapeutic strategy to target G4RNA prionoids.
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Biochimica et biophysica acta. Molecular cell research 1868(1) 118862-118862 2021年1月Spastin, a microtubule-severing AAA ATPase, regulates microtubule dynamics and plays important roles in cell division and neurogenesis. Mutations in the spastin-coding gene SPAST lead to neurodegenerative disorders and cause spastic paraplegia type 4. Spastin has two main isoforms, M1 and M87, that differ only in the presence or absence of 86 N-terminal amino acids and have alternative splicing variants that lack exon4. The N-terminal region of M1 contains a hydrophobic domain, nuclear localization signal (NLS), and nuclear export signal (NES), which partly explains the differences in the two isoforms' localization. However, the mechanisms involved in regulating isoform localization, and the effects of localization on spastin functions are not fully understood. We found endogenous M1 and M87 shuttled between the nucleus and cytoplasm during the cell cycle. We identified a NES (amino acids 195-204) that spans the microtubule-interacting and endosomal-trafficking domain and exon4 region. Furthermore, the NES sequence contains both the coiled-coil and exon4 region of spastin isoforms. Highly conserved leucine 195 in exon3 and the two residues in exon4 are crucial for predicted coiled-coil formation. Mutations in NES or leptomycin B treatment reduced cytoplasmic localization and microtubule fragmentation in M87 rather than in M1. Phosphomimetic mutation of threonine 306 adjacent to the NLS (amino acids 309-312) inhibited nuclear transport of M87. Our results indicate that the newly identified NES in the spastin isoforms containing exon4 regulates the subcellular localization of spastin in coordination with NLS controlled by the phosphorylation state of spastin, and is involved in microtubule severing.
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Journal of the neurological sciences 418 117151-117151 2020年11月15日
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Brain Research 1720 146289 2019年10月 査読有り
MISC
89-
JOURNAL OF THE NEUROLOGICAL SCIENCES 429 62-63 2021年10月
書籍等出版物
17-
In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1175/ 2019年9月
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厚生労働科学研究費 難治性疾患政策研究事業 「筋ジストロフィーの標準的医療普及のための調査研究」班 編 2019年4月
講演・口頭発表等
17-
9th International Conference on Unstable Microsatellites & Human Disease 2018年4月22日
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13th International Parkinson’s Disease Symposium in Takamatsu (iPDST) 2014年2月21日 招待有り
所属学協会
7Works(作品等)
22共同研究・競争的資金等の研究課題
12-
日本学術振興会 科学研究費助成事業 基盤研究(C) 2020年4月 - 2023年3月
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国立研究開発法人日本医療研究開発機構 難治性疾患実用化研究事業 2017年4月 - 2020年3月
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国立研究開発法人日本医療研究開発機構 難治性疾患実用化研究事業 2015年4月 - 2018年3月
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文部科学省科学研究費 挑戦的萌芽研究 2014年4月 - 2017年3月
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文部科学省科学研究費 基盤研究 (B) 2012年4月 - 2016年3月
産業財産権
1-
USPTO#6,885,497