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Affiliation |
Faculty of Medicine School of Medicine Department of Medical Sciences, Biochemistry and Molecular Biology |
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Assistant Professor |
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External Link |
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MURAO Naoya
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Research Areas 【 display / non-display 】
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Life Science / Neuroscience-general
Papers 【 display / non-display 】
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Sugiyama T, Murao N, Kadowaki H, Nishitoh H
Scientific reports 12 ( 1 ) 21840 2022.12
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports
There are no available therapies targeting the underlying molecular mechanisms of neurodegenerative diseases. Although chaperone therapies that alleviate endoplasmic reticulum (ER) stress recently showed promise in the treatment of neurodegenerative diseases, the detailed mechanisms remain unclear. We previously reported that mice with central nervous system-specific deletion of Derlin-1, which encodes an essential component for ER quality control, are useful as models of neurodegenerative diseases such as spinocerebellar degeneration. Cholesterol biosynthesis is essential for brain development, and its disruption inhibits neurite outgrowth, causing brain atrophy. In this study, we report a novel mechanism by which chemical chaperones ameliorate brain atrophy and motor dysfunction. ER stress was induced in the cerebella of Derlin-1 deficiency mice, whereas the administration of a chemical chaperone did not alleviate ER stress. However, chemical chaperone treatment ameliorated cholesterol biosynthesis impairment through SREBP-2 activation and simultaneously relieved brain atrophy and motor dysfunction. Altogether, these findings demonstrate that ER stress may not be the target of action of chaperone therapies and that chemical chaperone-mediated improvement of brain cholesterol biosynthesis is a promising novel therapeutic strategy for neurodegenerative diseases.
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Takashi Sugiyama, Naoya Murao, Hisae Kadowaki, Keizo Takao, Tsuyoshi Miyakawa, Yosuke Matsushita, Toyomasa Katagiri, Akira Futatsugi, Yohei Shinmyo, Hiroshi Kawasaki, Juro Sakai, Kazutaka Shiomi, Masamitsu Nakazato, Kohsuke Takeda, Katsuhiko Mikoshiba, Hidde L. Ploegh, Hidenori Ichijo, Hideki Nishitoh
iScience 24 ( 7 ) 102758 - 102758 2021.7
Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Elsevier BV
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Np95/Uhrf1 regulates tumor suppressor gene expression of neural stem/precursor cells, contributing to neurogenesis in the adult mouse brain. Reviewed
Murao N, Matsubara S, Matsuda T, Noguchi H, Mutoh T, Mutoh M, Koseki H, Namihira M, Nakashima K
Neuroscience research 143 31 - 43 2019.6
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
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Kimura A., Matsuda T., Sakai A., Murao N., Nakashima K.
Developmental Dynamics 247 ( 1 ) 229 - 238 2018.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Developmental Dynamics
© 2017 Wiley Periodicals, Inc. Background: Although quiescent neural stem cells (NSCs) in the adult hippocampus proliferate in response to neurogenic stimuli and subsequently give rise to new neurons continuously throughout life, misregulation of NSCs in pathological conditions, including aging, leads to the impairment of learning and memory. High mobility group B family 1 (HMGB1) and HMGB2, HMG family proteins that function as transcriptional activators through the modulation of chromatin structure, have been assumed to play some role in the regulation of adult NSCs; however, their precise functions and even expression patterns in the adult hippocampus remain elusive. Results: Here we show that expression of HMGB2 but not HMGB1 is restricted to the subset of NSCs and their progenitors. Furthermore, running, a well-known positive neurogenic stimulus, increased the proliferation of HMGB2-expressing cells, whereas aging was accompanied by a marked decrease in these cells. Intriguingly, HMGB2-expressing quiescent NSCs, which were shifted toward the proliferative state, were decreased as aging progressed. Conclusions: HMGB2 expression is strongly associated with transition from the quiescent to the proliferative state of NSCs, supporting the possibility that HMGB2 is involved in the regulation of adult neurogenesis and can be used as a novel marker to identify NSCs primed for activation in the adult hippocampus. Developmental Dynamics 247:229–238, 2018. © 2017 Wiley Periodicals, Inc.
DOI： 10.1002/dvdy.24559
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Role of the unfolded protein response in the development of central nervous system. Invited Reviewed
Murao N, Nishitoh H
The Journal of Biochemistry 162 ( 3 ) 155 - 162 2017.9
Language：English Publishing type：Research paper (scientific journal)
DOI： 10.1093/jb/mvx047
Books 【 display / non-display 】
Presentations 【 display / non-display 】
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ER quality is important for the homeostasis of adult hippocampal neural stem cells
Event date： 2022.11.30 - 2022.12.2
Presentation type：Symposium, workshop panel (public)
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記憶・学習などの高次脳機能を支える小胞体品質管理機構
村尾直哉、西頭英起
第15回日本臨床ストレス応答学会大会
Event date： 2022.11.5 - 2022.11.6
Presentation type：Symposium, workshop panel (nominated)
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中枢神経特異的Derlin-1欠損マウスの神経障害に対するケミカルシャペロンの作用メカニズム
杉山崇史、村尾直哉、西頭英起
第15回日本臨床ストレス応答学会大会
Event date： 2022.11.5 - 2022.11.6
Presentation type：Oral presentation (general)
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小胞体膜分子 Derlin-1の成体海馬ニューロン新生における役割
村尾直哉
第15回小胞体ストレス研究会 若手の会
Event date： 2022.7.29
Presentation type：Oral presentation (general)
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An endoplasmic reticulum protein Derlin-1 maintains neural stem cell populations in the adult hippocampus
村尾直哉、西頭英起
NEURO2022
Event date： 2022.6.30 - 2022.7.3
Presentation type：Poster presentation
Awards 【 display / non-display 】
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若手最優秀発表賞
2022.7 小胞体ストレス研究会
村尾直哉
Award type：Award from Japanese society, conference, symposium, etc.
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医学部長奨励賞
2022.3 宮崎大学医学部
村尾直哉
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優秀発表賞
2020.2 成体脳ニューロン新生懇談会
村尾直哉
Award type：Award from Japanese society, conference, symposium, etc.
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若手研究奨励賞
2017.11 臨床ストレス応答学会
村尾直哉
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
Grant-in-Aid for Scientific Research 【 display / non-display 】
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神経幹細胞の休眠状態の獲得を制御する小胞体品質管理機構の役割
Grant number： 22K06254 2022.04 - 2025.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
Authorship：Principal investigator
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病態脳における小胞体プロテオスタシス破綻によるコレステロール合成不全と脳萎縮
Grant number：22H02954 2022.04 - 2025.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(B)
Authorship：Coinvestigator(s)