Elucidation of mechanisms of prionoid conversion of alpha-synuclein by imaging mass spectrometry

• Project/Area Number: 17K19658
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine and related fields
• Research Institution: Osaka University
• Principal Investigator: Nagai Yoshitaka 大阪大学, 医学系研究科, 寄附講座教授 (60335354)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 脳神経疾患 / 蛋白質 / 脂質 / 分析科学 / 質量顕微鏡 / ショウジョウバエ / 質量分析顕微鏡

Outline of Final Research Achievements

In this study, we investigated the role of lipids on prionoid conversion and aggregation of α-synuclein (αSyn) in Parkinson’s disease and other synucleinopathies. We performed mass spectrometry imaging analyses of patients’ brains and identified some lipids that promote prionoid conversion of αSyn. We also established novel reporter flies for αSyn transmission in the brain.

Academic Significance and Societal Importance of the Research Achievements

本研究は、異なるバックグランドの研究者の協力を得て、質量分析イメージングなど最先端の物理化学的技術の医学・生物学への導入を促進するという点で、挑戦的研究としての意義が高い。本研究により、蛋白質プリオノイド化の誘因として脂質の役割りが明らかになり、その構造多様性が疾患多様性を引き起こすメカニズムは、アルツハイマー病や前頭側頭型認知症など他の神経変性疾患にも共通する可能性がある。

Research Products

• [Journal Article] Arginine is a disease modifier of polyQ disease models that stabilizes polyQ protein conformation. (2020)
  • Author(s): Minakawa E.N., et al.
  • Journal Title: Brain Volume: in press
  • Peer Reviewed
• [Journal Article] 神経変性疾患とエクソソーム (2020)
  • Author(s): 武内敏秀、永井義隆
  • Journal Title: 医学のあゆみ Volume: 272 Pages: 319-324
• [Journal Article] ショウジョウバエモデルを用いたALSの病態解明と治療法開発 (2020)
  • Author(s): 田港朝也、永井義隆
  • Journal Title: 医学のあゆみ Volume: 272 Pages: 535-540
• [Journal Article] Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid. (2019)
  • Author(s): 2. Kakuda K, Ikenaka K, Araki K, So M, Aguirre C, Kajiyama Y, Konaka K, Noi K, Baba K, Tsuda H, Nagano S, Ohmichi T, Nagai Y, Tokuda T, El-Agnaf O, Ogi H, Goto Y, Mochizuki H.
  • Journal Title: Sci Rep Volume: 9 Issue: 1 Pages: 6001-6001
  • DOI: 10.1038/s41598-019-42399-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] E46K mutantα-synuclein is more degradation resistant and exhibits greater toxic effects than wild-typeα-synuclein in Drosophila models of Parkinson's disease. (2019)
  • Author(s): R. Sakai, M. Suzuki, M. Ueyama, T. Takeuchi, E. N. Minakawa, H. Hayakawa, K. Baba, H. Mochizuki, Y. Nagai
  • Journal Title: PLoS ONE Volume: 14 Issue: 6 Pages: e0218261-e0218261
  • DOI: 10.1371/journal.pone.0218261
  • Peer Reviewed / Open Access
• [Journal Article] Arylsulfatase A, a genetic modifier of Parkinson's disease, is an α-synuclein chaperone. (2019)
  • Author(s): J. S. Lee, K. Kanai, M. Suzuki, W. S. Kim, H. S. Yoo, Y. Fu, D-K. Kim, B. C. Jung, M. Choi, K. W. Oh, Y. Li, M. Nakatani, T. Nakazato, S. Sekimoto, M. Furuyama, H. Yoshino, S. Kubo, K. Nishioka, R. Sakai, M. Ueyama, H. Mochizuki, H-J. Lee, S. P. Sardi, G. M. Halliday, Y. Nagai, P. H. Lee, N. Hattori, S-J. Lee
  • Journal Title: Brain Volume: 142 Issue: 9 Pages: 2845-59
  • DOI: 10.1093/brain/awz205
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Parkinson’s disease is a type of amyloidosis featuring accumulation of amyloid fibrils of α-synuclein (2019)
  • Author(s): Araki Katsuya、Yagi Naoto、Aoyama Koki、Choong Chi-Jing、Hayakawa Hideki、Fujimura Harutoshi、Nagai Yoshitaka、Goto Yuji、Mochizuki Hideki
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 116 Issue: 36 Pages: 17963-17969
  • DOI: 10.1073/pnas.1906124116
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The lncRNA hsrω regulates arginine dimethylation of FUS to cause its proteasomal degradation in Drosophila. (2019)
  • Author(s): *Lo Piccolo L., Mochizuki H., *Nagai Y.
  • Journal Title: J. Cell Sci. Volume: 132 Issue: 20
  • DOI: 10.1242/jcs.236836
  • Peer Reviewed / Open Access
• [Journal Article] Lipids as trans-acting effectors for α-synuclein in the pathogenesis of Parkinson’s disease (2019)
  • Author(s): Ikenaka K, Suzuki M, Mochizuki H, Nagai Y
  • Journal Title: Frontiers in Neuroscience Volume: 13 Pages: 693-693
  • DOI: 10.3389/fnins.2019.00693
  • Peer Reviewed / Open Access
• [Journal Article] Molecular mechanisms and future therapeutics for spinocerebrellar ataxia type 31 (SCA31). (2019)
  • Author(s): *Ishikawa K., Nagai Y.
  • Journal Title: Neurotherapeutics Volume: 16 Issue: 4 Pages: 1106-1114
  • DOI: 10.1007/s13311-019-00804-6
  • Peer Reviewed / Open Access
• [Journal Article] Structurally Distinct α‐Synuclein Fibrils Induce Robust Parkinsonian Pathology (2019)
  • Author(s): Hayakawa Hideki、Nakatani Rie、Ikenaka Kensuke、Aguirre Cesar、Choong Chi‐Jing、Tsuda Hiroshi、Nagano Seiichi、Koike Masato、Ikeuchi Takeshi、Hasegawa Masato、Papa Stella M.、Nagai Yoshitaka、Mochizuki Hideki、Baba Kousuke
  • Journal Title: Movement Disorders Volume: 35 Issue: 2 Pages: 256-267
  • DOI: 10.1002/mds.27887
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 脊髄小脳変性症に対するポリグルタミン蛋白質のミスフォールディング・凝集を標的とした分子治療 (2019)
  • Author(s): 永井義隆
  • Journal Title: Clinical Neuroscience Volume: 37 Pages: 1015-1018
• [Journal Article] RNA結合タンパクと病態機序 (2019)
  • Author(s): 石川欽也、石黒太郎、佐藤望、永井義隆
  • Journal Title: 神経内科 Volume: 91 Pages: 458-464
• [Journal Article] 神経変性疾患に関わるリピート関連非ATG依存性翻訳と低複雑性ドメイン (2019)
  • Author(s): 上山盛夫、永井義隆
  • Journal Title: 実験医学 Volume: 37 Pages: 3070-3076
• [Journal Article] Sleep Disturbance as a Potential Modifiable Risk Factor for Alzheimer’s Disease (2019)
  • Author(s): Minakawa Eiko、Wada Keiji、Nagai Yoshitaka
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 4 Pages: 803-803
  • DOI: 10.3390/ijms20040803
  • Peer Reviewed / Open Access
• [Journal Article] Supplemental Treatment for Huntington’s Disease with miR-132 that Is Deficient in Huntington’s Disease Brain (2018)
  • Author(s): Fukuoka Masashi、Takahashi Masaki、Fujita Hiromi、Chiyo Tomoko、Popiel H. Akiko、Watanabe Shoko、Furuya Hirokazu、Murata Miho、Wada Keiji、Okada Takashi、Nagai Yoshitaka、Hohjoh Hirohiko
  • Journal Title: Mol. Ther. Nucleic Acids Volume: 11 Pages: 79-90
  • DOI: 10.1016/j.omtn.2018.01.007
  • Peer Reviewed / Open Access
• [Journal Article] NPM-hMLF1 fusion protein suppresses defects of a Drosophila FTLD model expressing the human FUS gene. (2018)
  • Author(s): Yamamoto I, Azuma Y, Kushimura Y, Yoshida H, Mizuta I, Mizuno T, Ueyama M, Nagai Y, Tokuda T, Yamaguchi M.
  • Journal Title: Sci. Rep. Volume: 8 Issue: 1 Pages: 11291-11291
  • DOI: 10.1038/s41598-018-29716-9
  • Peer Reviewed / Open Access
• [Journal Article] Hippo, Drosophila MST, is a novel modifier of motor neuron degeneration induced by knockdown of Caz, Drosophila FUS. (2018)
  • Author(s): Azuma Y, Tokuda T, Kushimura Y, Yamamoto I, Mizuta I, Mizuno T, Nakagawa M, Ueyama M, Nagai Y, Iwasaki Y, Yoshida M, Pan D, Yoshida H, Yamaguchi M.
  • Journal Title: Exp Cell Res. Volume: 371 Issue: 2 Pages: 311-321
  • DOI: 10.1016/j.yexcr.2018.08.001
  • Peer Reviewed / Open Access
• [Journal Article] Developing biomarkers for neurodegenerative diseases using genetically-modified common marmoset models (2018)
  • Author(s): Tomioka Ikuo、Nagai Yoshitaka、Seki Kazuhiko
  • Journal Title: Neural Regeneration Research Volume: 13 Issue: 7 Pages: 1189-1189
  • DOI: 10.4103/1673-5374.235028
  • Peer Reviewed
• [Journal Article] Parkinson’s disease-linked DNAJC13 mutation aggravates α-synuclein-induced neurotoxicity through perturbation of endosomal trafficking. (2018)
  • Author(s): Yoshida S, Hasegawa T, Suzuki M, Sugeno N, Kobayashi J, Ueyama M, Fukuda M, Ido-Fujibayashi A, Sekiguchi K, Ezura M, Kikuchi A, Baba T, Takeda A, Mochizuki H, Nagai Y and Aoki M.
  • Journal Title: Hum Mol Genet. Volume: 27 Issue: 5 Pages: 823-836
  • DOI: 10.1093/hmg/ddy003
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of ter94, Drosophila VCP, improved motor neuron degeneration induced by knockdown of TBPH, Drosophila TDP-43. (2018)
  • Author(s): Kushimura Y., Tokuda T., Azuma Y., Yamamoto I., Mizuta I., Mizuno T., Nakagawa M., Ueyama M., Nagai Y., Yoshida H., Yamaguchi M.
  • Journal Title: Am. J. Neurodegener. Dis. Volume: 1 Pages: 11-31
  • Peer Reviewed
• [Journal Article] A spontaneously immortalized Schwann cell line from aldose reductase-deficient mice as a useful tool for studying polyol pathway and aldehyde metabolism. (2018)
  • Author(s): 2.Niimi N, Yako H, Takaku S, Kato H, Matsumoto T, Nishito Y, Watabe K, Ogasawara S, Mizukami H, Yagihashi S, Chung SK, Sango K.
  • Journal Title: Journal of Neurochemistry Volume: 印刷中 Pages: 97-106
  • DOI: 10.1016/j.neuint.2017.12.014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chronic sleep fragmentation exacerbates amyloid β deposition in Alzheimer’s disease model mice (2017)
  • Author(s): Minakawa Eiko N.、Miyazaki Koyomi、Maruo Kazushi、Yagihara Hiroko、Fujita Hiromi、Wada Keiji、Nagai Yoshitaka
  • Journal Title: Neurosci. Lett. Volume: 653 Pages: 362-369
  • DOI: 10.1016/j.neulet.2017.05.054
  • Peer Reviewed / Open Access
• [Journal Article] Generation of transgenic marmosets using a tetracyclin-inducible transgene expression system as a neurodegenerative disease model† (2017)
  • Author(s): Tomioka Ikuo、Nogami Naotake、Nakatani Terumi、Owari Kensuke、Fujita Naoko、Motohashi Hideyuki、Takayama Osamu、Takae Kentaro、Nagai Yoshitaka、Seki Kazuhiko
  • Journal Title: Biol. Reprod. Volume: 97 Issue: 5 Pages: 772-780
  • DOI: 10.1093/biolre/iox129
  • Peer Reviewed
• [Journal Article] FUS toxicity is rescued by the modulation of lncRNA hsrω expression in Drosophila melanogaster. (2017)
  • Author(s): Piccolo, L. L., Jantrapirom, S., Nagai, Y. and Yamaguchi M.
  • Journal Title: Sci. Rep. Volume: 7(1) Issue: 1 Pages: 15660-15660
  • DOI: 10.1038/s41598-017-15944-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Commentary: p62 plays a protective role in the autophagic degradation of polyglutamine protein oligomers in polyglutamine disease model flies. (2017)
  • Author(s): Saitoh Y., Nagai Y.
  • Journal Title: J. Rare Dis. Res. & Treat. Volume: 2 Pages: 7-10
  • Peer Reviewed
• [Journal Article] Protein Misfolding and Aggregation as a Therapeutic Target for Polyglutamine Diseases (2017)
  • Author(s): Takeuchi Toshihide、Nagai Yoshitaka
  • Journal Title: Brain Sci. Volume: 7 Issue: 10 Pages: 128-128
  • DOI: 10.3390/brainsci7100128
  • Peer Reviewed / Open Access
• [Journal Article] ショウジョウバエを用いたパーキンソン病の病態解析 (2017)
  • Author(s): 堺竜介、鈴木マリ、永井義隆
  • Journal Title: 医学のあゆみ Volume: 262 Pages: 641-646
• [Journal Article] 良好な睡眠を通じた認知症の発症・進展予防の可能性 (2017)
  • Author(s): 皆川栄子、和田圭司、永井義隆
  • Journal Title: 実験医学 Volume: 35 Pages: 2091-2094
• [Presentation] 神経変性疾患ポリグルタミン病に対するタンパク質凝集阻害薬QAI1の同定とその治療効果 (2020)
  • Author(s): 永井義隆、皆川栄子、ポピエルヘレナ明子、山根宏志、他田正義、高橋俊昭、武内敏秀、望月秀樹、戸田達史、和田圭司、小野寺理
  • Organizer: 第93回 日本薬理学会
• [Presentation] Identification of proteins in the cerebrospinal fluid of patients with Parkinson’s Disease that are associated with impaired sleep quality. (2020)
  • Author(s): Minakawa E.N., Yagihara H., Saitoh Y., Miyazaki M., Tsuru A., Suzuki M., Kamei Y., Ueda K., Wada K., Nagai Y.
  • Organizer: Takeda Expert Conference on Parkinson's Disease
  • Int'l Joint Research
• [Presentation] ショウジョウバエモデルを活用した効率的な神経変性疾患研究 (2019)
  • Author(s): 永井義隆
  • Organizer: 第42回 日本神経科学会・第62回 日本神経化学会合同大会
  • Invited
• [Presentation] 筋萎縮性側索硬化症におけるストレス顆粒形成と異常タンパク質凝集 (2019)
  • Author(s): 永井義隆
  • Organizer: 第92回 日本生化学会
  • Invited
• [Presentation] 液-液相分離（LLPS）と非膜性オルガネラが関わる神経変性疾患の病態解明へ向けて (2019)
  • Author(s): 永井義隆
  • Organizer: 第38回 日本認知症学会学術集会
  • Invited
• [Presentation] 認知症・神経変性疾患バイオマーカーとしての血液中エクソソームの可能性 (2019)
  • Author(s): 永井義隆
  • Organizer: 第38回 日本認知症学会学術集会
  • Invited
• [Presentation] RNAシャペロンとしてのTDP-43の新機能：異常伸長UGGAAリピートRNA凝集とリピート関連翻訳の制御による神経変性抑制 (2019)
  • Author(s): 永井義隆、石川欽也
  • Organizer: 第42回 分子生物学会
  • Invited
• [Presentation] Prion-like conformational transmission of polyglutamine protein. (2019)
  • Author(s): 小澤大作、武内敏秀、永井義隆
  • Organizer: 第60回 日本神経学会学術大会
• [Presentation] E46K α-synuclein mutation gains resistance to degradation, leading to enhanced toxicity in PD flies. (2019)
  • Author(s): 堺竜介、鈴木マリ、上山盛夫、武内敏秀、望月秀樹、永井義隆
  • Organizer: 第60回 日本神経学会学術大会
• [Presentation] hnRNPA3 alleviates the GGGGCC toxicity in C9orf72-linked ALS / FTD model Drosophila. (2019)
  • Author(s): 田港朝也、上山盛夫、森康治、池田学、永井義隆
  • Organizer: 第60回 日本神経学会学術大会
• [Presentation] Monitoring repeat-associated non-AUG (RAN) translation toward drug screening for ALS/FTD. (2019)
  • Author(s): 橋本茜、武内敏秀、上山盛夫、森康治、池田学、永井義隆
  • Organizer: 第60回 日本神経学会学術大会
• [Presentation] Spt4 knockdown suppressed SCA31-linked expanded UGGAA repeat-induced toxicity in Drosophila. (2019)
  • Author(s): 石黒太郎、横田隆徳、石川欽也、永井義隆、Petrucelli L.
  • Organizer: 第60回 日本神経学会学術大会
• [Presentation] Pathological roles of expanded repeat RNA and dipeptide repeat proteins in C9-ALS/FTD model fly. C9orf72関連筋萎縮性側索硬化症/前頭側頭型認知症モデルショウジョウバエにおける異常伸長リピートRNAとジペプチドリピートタンパク質の病態での役割 (2019)
  • Author(s): 上山盛夫、石黒太郎、今野卓哉、小山哲秀、石川欽也、和田圭司、小野寺理、永井義隆
  • Organizer: 第42回 日本神経科学会・第62回 日本神経化学会合同大会
• [Presentation] SCA36モデルショウジョウバエの樹立 (2019)
  • Author(s): 田港朝也、上山盛夫、山下徹、池田佳生、阿部康二、永井義隆
  • Organizer: 第42回 日本神経科学会・第62回 日本神経化学会合同大会
• [Presentation] Identification of proteins associated with impairment of sleep quality in cerebrospinal fluids of Parkinson’s disease patients. (2019)
  • Author(s): 皆川栄子、八木原紘子、齊藤勇二、宮崎将行、都留あゆみ、鈴木みのり、亀井雄一、植田幸嗣、和田圭司、永井義隆
  • Organizer: 第42回 日本神経科学会・第62回 日本神経化学会合同大会
• [Presentation] 変異型α-シヌクレインフィブリルによるマウス脳でのレビー病理の形成 (2019)
  • Author(s): 馬場孝輔、早川英規、池中建介、Choong Chi-Jing、津田浩史、小池正人、長野清一、池内健、長谷川成人、永井義隆、望月秀樹
  • Organizer: 第42回 日本神経科学会・第62回 日本神経化学会合同大会
• [Presentation] In vitroにおけるalpha-synuclein細胞外分泌機構の検討 (2019)
  • Author(s): 早川英規、馬場孝輔、Choong Chi-Jing、池中建介、武内敏秀、永井義隆、望月秀樹
  • Organizer: 第42回 日本神経科学会・第62回 日本神経化学会合同大会
• [Presentation] 孤発性パーキンソン病遺伝子MCCC1におけるパーキンソン病発症メカニズム解析 (2019)
  • Author(s): 曽我部俊策、佐竹渉、小笠原佑介、中野浩子、上山盛夫、鈴木マリ、松本隆作、浜口哲矢、土井大輔、村山繁雄、高橋淳、青井貴之、永井義隆、戸田達史
  • Organizer: 第42回 日本神経科学会・第62回 日本神経化学会合同大会
• [Presentation] E46K α-synuclein mutation confers degradation resistance in Parkinson’s disease model flies. (2019)
  • Author(s): 堺竜介、鈴木マリ、上山盛夫、武内敏秀、望月秀樹、永井義隆
  • Organizer: 第13回 パーキンソン病・運動障害疾患コングレス
• [Presentation] ポリグルタミン蛋白質によるプリオン様異常構造伝播 (2019)
  • Author(s): 小澤大作、武内敏秀、永井義隆
  • Organizer: 第7回 日本アミロイドーシス研究会
• [Presentation] ポリグルタミン蛋白質によるプリオン様異常構造伝播 (2019)
  • Author(s): 小澤大作、武内敏秀、永井義隆
  • Organizer: 第14回 日本臨床ストレス応答学会
• [Presentation] C9-ALS/FTDモデルショウジョウバエにおけるリピート関連非ATG翻訳の制御 (2019)
  • Author(s): 上山盛夫、石黒太郎、Gendron T.F.、今野卓哉、小山哲秀、和田圭司、石川欽也、小野寺理、Petrucelli L.、永井義隆
  • Organizer: 第38回 日本認知症学会
• [Presentation] hnRNPA3はC9orf72関連FTDモデルショウジョウバエのリピートRNA毒性を軽減する (2019)
  • Author(s): 田港朝也、上山盛夫、森康治、池田学、永井義隆
  • Organizer: 第38回 日本認知症学会
• [Presentation] 運動は血漿由来エクソソーム分泌を亢進させる (2019)
  • Author(s): 武田明子、武内敏秀、皆川栄子、永井義隆
  • Organizer: 第42回 分子生物学会
• [Presentation] 国立精神・神経医療研究センターにおけるトランスジェニックマーモセット研究の現状 (2019)
  • Author(s): 中谷輝実、小杉亮人、小泉昌司、小島潮子、川野邊哲代、野上尚武、尾張健介、沼澤秀美、皆川栄子、武内敏秀、富岡郁夫、齊藤祐子、花川隆、永井義隆、和田圭司 、関和彦
  • Organizer: 第9回 日本マーモセット研究会
• [Presentation] Structural basis of polyglutamine protein aggregation. (2019)
  • Author(s): Nagai Y.
  • Organizer: The 3rd Ulm Meeting; Biophysics of Amyloid Formation
  • Int'l Joint Research / Invited
• [Presentation] Therapeutic strategy for the polyglutamine diseases targeting protein misfolding and aggregation. (2019)
  • Author(s): Nagai Y.
  • Organizer: University of Gottingen, DZNE Seminar
  • Int'l Joint Research / Invited
• [Presentation] Evidence for prion-like conformational transmission of a polyglutamine protein monomer. (2019)
  • Author(s): Nagai Y., Ozawa D., Takeuchi T.
  • Organizer: 10th Gordon Research Conference on CAG Triplet Repeat Disorders
  • Int'l Joint Research / Invited
• [Presentation] Disease-modifying therapy for the polyglutamine diseases targeting protein misfolding and aggregation. (2019)
  • Author(s): Nagai Y.
  • Organizer: The JSPS Core-toCore Program Seminar; Towards a cure for amyloid diseases
  • Int'l Joint Research / Invited
• [Presentation] Dysfunction in an autophagy-lysosome degradation pathway promotes secretion of ubiquitinated proteins via extracellular vesicles. (2019)
  • Author(s): Takeuchi T., Sakai S., Ando H., Nagai Y.
  • Organizer: Annual Meeting of International Society for Extracellular Vesicles (ISEV2019)
  • Int'l Joint Research
• [Presentation] Comparison of serum and plasma as a source of blood extracellular vesicles reveals possible contamination of serum with platelet-derived particles produced during coagulation. (2019)
  • Author(s): Zhang X., Takeuchi T., Nagai Y.
  • Organizer: Annual Meeting of International Society for Extracellular Vesicles (ISEV2019)
  • Int'l Joint Research
• [Presentation] Identification of cerebrospinal fluid proteins associated with impaired sleep quality in Parkinson’s disease. (2019)
  • Author(s): Minakawa E.N., Yagihara H., Saitoh Y., Tsuru A., Kamei Y., Ueda K., Wada K., Nagai Y.
  • Organizer: The 5th World Parkinson Congress (WPC 2019)
  • Int'l Joint Research
• [Presentation] Prion-like conformational transmission between polyglutamine protein monomers. (2019)
  • Author(s): Ozawa D., Takeuchi T., Nagai Y.
  • Organizer: Asia Pacific Prion Symposium 2019
  • Int'l Joint Research
• [Presentation] Conformational transmission between polyglutamine protein monomers. (2019)
  • Author(s): Ozawa D., Takeuchi T., Nagai Y.
  • Organizer: The JSPS Core-toCore Program Seminar; Towards a cure for amyloid diseases
  • Int'l Joint Research
• [Presentation] Establishment of slowly progressive Parkinson's disease marmoset model by α-synuclein fibril injection. (2018)
  • Author(s): Yabumoto T., Baba K., Hayakawa H., Yoshida F., Uehara T., Nakatani R., Ikenaka K., Tsuda H., Nagano S., Nagai Y., Hamanaka H., Hirata M., Mochizuki H.
  • Organizer: The 143rd Annual Meeting of the American Neurological Association
  • Int'l Joint Research
• [Presentation] Establishment of α-synuclein transgenic Drosophila model by site-specific transgenesis. (2018)
  • Author(s): 堺竜介、鈴木マリ、上山盛夫、武内敏秀、永井義隆、望月秀樹
  • Organizer: 第59回 日本神経学会学術大会
• [Presentation] DNAJC13 mutation aggravates alpha-synuclein-induced toxicity through perturbation of trafficking. (2018)
  • Author(s): 吉田隼、長谷川隆文、鈴木マリ、菅野直人、小林潤平、上山盛夫、福田光則、藤林明美、関口清俊、江面道典、菊池昭夫、馬場徹、武田篤、望月秀樹、永井義隆、青木正志
  • Organizer: 第59回 日本神経学会学術大会
• [Presentation] 迅速化凝集アッセイと線虫モデルの組み合わせによるシヌクレイン凝集阻害薬スクリーニング (2018)
  • Author(s): 池中建介、角田渓太、馬場孝輔、荒木克哉、武内敏秀、園田静夏、永井義隆、後藤祐児、望月秀樹
  • Organizer: 第12回 パーキンソン病・運動障害疾患コングレス
• [Presentation] α-synuclein aggregation and propagation in the marmoset brain deteriorates its motor function. (2018)
  • Author(s): 薮本大紀、馬場孝輔、早川英規、池中建介、吉田史章、上原拓也、仲谷利栄、宮内英昭、津田浩史、長野清一、濱中裕喜、永井義隆、平田雅之、望月秀樹
  • Organizer: 第41回 日本神経科学会
• [Presentation] Regulatory role of TDP-43 as an RNA chaperone for RNA aggregation and repeat-associated translation in SCA31. (2017)
  • Author(s): Nagai Y., Ishikawa K.
  • Organizer: 2nd International symposium “Brain Protein Aging and Dementia Control”
  • Int'l Joint Research / Invited
• [Presentation] Dietary restriction improves misfolding protein-related neurodegeneration in Drosophila. (2017)
  • Author(s): Suzuki M., Neumann A.-M. Saitoh Y. Fujikake N., Wada K., Sango K., Nagai Y.
  • Organizer: Keystone Symposia on Aging and and Mechanisms of Aging-Related Disease
  • Int'l Joint Research
• [Presentation] p62/SQSTM1 contributes to the autophagic clearance of toxic protein oligomers in neurodegenerative diseases. (2017)
  • Author(s): Nagai Y., Saitoh Y.
  • Organizer: The 8th International Symposium on Autophagy
  • Int'l Joint Research
• [Presentation] Dietary restriction improves neurodegeneration in Drosophila models of neurodegenerative diseases. (2017)
  • Author(s): Suzuki M., Neumann A.-M. Saitoh Y. Fujikake N., Wada K., Sango K., Nagai Y.
  • Organizer: EMBO Symposium on Mechanisms of Neurodegeneration
  • Int'l Joint Research
• [Presentation] Regulatory role of RNA chaperone for noncoding repeat RNA aggregation and repeat-associated translation in SCA31. (2017)
  • Author(s): Nagai Y., Ishiguro T., Sato N., Ueyama M., Fujikake N., Yokota T., Wada K., Mizusawa H., Ishikawa K.
  • Organizer: The 43rd Naito Conference on Noncoding RNA：Biology, Chemistry, & Diseases
  • Int'l Joint Research
• [Presentation] Transgenic monkey model of the polyglutamine diseases recapitulating progressive neurological symptoms and polyglutamine protein inclusions. (2017)
  • Author(s): Nagai Y., Tomioka I., Ishibashi H., Minakawa E.N, Motohashi H.H., Takayama O., Saito Y., Popiel H.A., Puentes S., Owari K., Nakatani T., Nogami N., Yamamoto K., Noguchi S., Nagano S., Nishino I., Ichinohe N., Wada K., Kohsaka S., Seki K.
  • Organizer: The 23rd World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] Induction of exosome secretion and its proteomic changes in the polyglutamine disease models. (2017)
  • Author(s): Takeuchi T., Kanai M., Ueda K., Takafuji K., Sakai S., Nagai Y.
  • Organizer: The 23rd World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] Repeat associated non-ATG translation and its regulation in C9orf72-associated amyotrophic lateral sclerosis/frontotemporal dementia model fly. (2017)
  • Author(s): Ueyama M., Ishiguro T., Konno T., Koyama A., Wada K., Ishikawa K., Onodera O., Nagai Y.
  • Organizer: The 23rd World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] Chronic sleep fragmentation accelerates amyloid β pathology in Alzheimer’s disease model mice. (2017)
  • Author(s): Minakawa E.N., Miyazaki K., Maruo K., Yagihara H., Fujita H., Wada K., Nagai Y.
  • Organizer: The 23rd World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] Improvement of misfolding protein-induced neurodegeneration by dietary restriction in Drosophila. (2017)
  • Author(s): Suzuki M., Neumann A.-M. Saitoh Y. Fujikake N., Wada K., Sango K., Nagai Y.
  • Organizer: The 23rd World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] Balance between RNA binding proetin TDP-43 and an RNA UGGAA repeat underlies pathogenesis of spinocerebellar ataxia type 31 (SCA31) and motor neuron disease fly models. (2017)
  • Author(s): Ishiguro T., Sato N., Ueyama M., Fujikake N., Sellier C., Tokuda E., Zamiri B., Gall-Duncan T., Mirceta M., Furukawa Y., Yokota T., Wada K., Taylor J.P., Pearson C.E., Charlet-Berguerand N., Mizusawa H., Nagai Y., Ishikawa K.
  • Organizer: The 23rd World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] Parkinson’s disease-linked DNAJC13 mutation aggravates α-synuclein-induced neurotoxicity through perturbation of endosomal trafficking. (2017)
  • Author(s): Hasegawa T., Yoshida S., Suzuki M., Sugeno N., Kobayashi J., Ueyama M., Ezura M., Kikuchi A., Baba T., Takeda A., Mochizuki H., Nagai Y., Aoki M.
  • Organizer: The 23rd World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] Identification of target mRNA transported to axons by TDP-43. (2017)
  • Author(s): Nagano S., Ueyama M., Mochizuki H., Nagai Y., Araki T.
  • Organizer: The 23rd World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] Fine structural analysis of α-synuclein aggregates in patient’s brain with synchrotron radiation. (2017)
  • Author(s): Araki K., Yagi N., Ikenaka K., Hayakawa H., Baba K., Nagai Y., Mochizuki H.
  • Organizer: The 23rd World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] In vitro assessment of extracellular α-synuclein secretion. (2017)
  • Author(s): Hayakawa H., Baba K., Takeuchi T., Choong C.J., Nagano S., Nagai Y., Hagihara K., Mochizuki H.
  • Organizer: The 23rd World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] Go-Sha-Jinki-Gan (GJG) palliates inflammation in experimental autoimmune encephalomyelitis (EAE) mice. (2017)
  • Author(s): Jiang S., Baba K., Okuno T., Hayakawa H., Ikenaka K., Sasaki T., Nagano S., Nagai Y., Hagihara K., Mochizuki H.
  • Organizer: The 23rd World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] The search for genes that modulate FUS-mediated phenotypes by Drosophila amyotrophic lateral sclerosis model. (2017)
  • Author(s): Azuma Y., Tokuda T., Kushimura Y., Yamamoto I., Yoshida H., Mizuta I., Ueyama M., Nagai Y., Nakagawa M., Mizuno T., Yamaguchi M.
  • Organizer: The 23rd World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] Loss of function mutant of ter94, Drosophila VCP, partially enhanced motor neuron degeneration induced by knockdown of TBPH, Drosophila TDP-43. (2017)
  • Author(s): Kushimura Y., Tokuda T., Azuma Y., Yamamoto I., Yoshida H., Mizuta I., Ueyama M., Nagai Y., Nakagawa M., Mizuno T., Yamaguchi M.
  • Organizer: The 23rd World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] Generation of transgenic monkey with tetracyclin-inducible gene expression system for neurodegenerative disease model. (2017)
  • Author(s): 18.Tomioka I., Nogami N., Fujita N., Owari K., Nakatani T., Motohashi H., Takayama O., Nagai Y., Seki K.
  • Organizer: The 23rd World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] The search for genes that modulate FUS-mediated phenotypes by Drosophila amyotrophic lateral sclerosis model. (2017)
  • Author(s): Azuma Y., Tokuda T., Kushimura Y., Yamamoto I., Ueoka I., Mizuta I., Mizuno T., Nakagawa M., Ueyama M., Nagai Y., Yoshida H., Yamaguchi M.
  • Organizer: CSHL 2017 Neurobiology of Drosophila
  • Int'l Joint Research
• [Presentation] Loss of function mutant of ter94, Drosophila VCP, partially enhanced motor neuron degeneration induced by knockdown of TBPH, Drosophila TDP-43. (2017)
  • Author(s): Kushimura Y., Tokuda T., Azuma Y., Yamamoto I., Ueoka I., Mizuta I., Mizuno T., Nakagawa M., Ueyama M., Nagai Y., Yoshida H., Yamaguchi M.
  • Organizer: CSHL 2017 Neurobiology of Drosophila
  • Int'l Joint Research
• [Presentation] Regulatory role of RNA chaperone TDP-43 for RNA misfolding and repeat-associated translation in SCA31. (2017)
  • Author(s): Ishikawa K., Ishiguro T., Sato N., Ueyama M., Fujikake N., Sellier C., Tokuda E., Zamiri B., Gall-Duncan T., Mirceta M., Furukawa Y., Yokota T., Wada K., Taylor J.P., Pearson C.E., Charlet-Berguerand N., Mizusawa H., Nagai Y.
  • Organizer: 67th Annual Meeting of American Society of Human Genetics
  • Int'l Joint Research
• [Presentation] 遺伝子改変技術を用いた精神・神経疾患モデル霊長類の作出と評価 (2017)
  • Author(s): 関和彦、富岡郁夫、永井義隆、斎藤裕子、石橋英俊、花川隆、尾張健介、野上尚武、小泉昌司、皆川栄子、中谷輝美、川野邊哲代
  • Organizer: 第58回日本神経病理学会 (シンポジウム)
  • Invited
• [Presentation] リピート関連非ATG依存性翻訳の制御による筋委縮性側索硬化症の病態メカニズム解明 (2017)
  • Author(s): 永井義隆、上山盛夫
  • Organizer: 第40回日本神経科学会 (シンポジウム)
  • Invited
• [Presentation] 分子シャペロンはエクソソームを介した細胞間伝播によりポリグルタミン病に対して細胞非自律的な治療効果を発揮する (2017)
  • Author(s): 永井義隆
  • Organizer: 第60回 日本神経化学会（シンポジウム）
  • Invited
• [Presentation] The structure analysis for α-synuclein and Lewy bodies in the brain of Parkinson’s disease patients with synchrotron radiation. (2017)
  • Author(s): 荒木克哉、八木直人、池中健介、早川英規、馬場孝輔、永井義隆、後藤祐児、望月秀樹
  • Organizer: 第60回 日本神経化学会（シンポジウム）
  • Invited
• [Presentation] Elucidating the pathological mechanisms of amyotrophic lateral sclerosis/ frontotemporal dementia using Drosophila models. (2017)
  • Author(s): 上山盛夫、永井義隆
  • Organizer: 第89回 日本遺伝学会大会 (受賞講演)
  • Invited
• [Presentation] パーキンソン病におけるαシヌクレイン-脂質相互作用の役割 (2017)
  • Author(s): 鈴木マリ、永井義隆
  • Organizer: 第12回 臨床ストレス応答学会（シンポジウム）
  • Invited
• [Presentation] エクソソームを介する非細胞自律的な蛋白質凝集・神経変性の抑制 (2017)
  • Author(s): 永井義隆
  • Organizer: 第36回 日本認知症学会学術集会（学会賞受賞講演）
  • Invited
• [Presentation] Glucocerebrosidase（GBA）遺伝子変異によるパーキンソン病の発症メカニズム (2017)
  • Author(s): 永井義隆、鈴木マリ
  • Organizer: 第40回 日本分子生物学会・第90回 日本生化学会（ワークショップ）
  • Invited
• [Presentation] 細胞外小胞の分泌・伝播を介した生体内プロテオスタシス制御 (2017)
  • Author(s): 武内敏秀、永井義隆
  • Organizer: 第40回 日本分子生物学会・第90回 日本生化学会（ワークショップ）
  • Invited
• [Presentation] 中途覚醒の増加はアルツハイマー病モデルマウスのアミロイドβ病理を悪化させる (2017)
  • Author(s): 皆川栄子、宮崎歴、丸尾和司、盆子原紘子、藤田寛美、和田圭司、永井義隆
  • Organizer: 第42回 日本睡眠学会
• [Presentation] C9orf72関連筋萎縮性側索硬化症/前頭側頭型認知症モデルショウジョウバエにおけるリピート関連非ATG翻訳の制御 (2017)
  • Author(s): 上山盛夫、石黒太郎、藤掛伸宏、今野卓哉、小山哲秀、小野寺理、石川欽也、和田圭司、永井義隆
  • Organizer: 第40回 日本神経科学会
• [Presentation] 中途覚醒の増加はアルツハイマー病モデルマウスのアミロイドβ病理を悪化させる (2017)
  • Author(s): 皆川栄子、宮崎歴、丸尾和司、盆子原紘子、藤田寛美、和田圭司、永井義隆
  • Organizer: 第40回 日本神経科学会
• [Presentation] ポリグルタミン病モデルマーモセットのライン化及び表現型解析 (2017)
  • Author(s): 野上尚武、尾張健介、中谷輝美、小泉昌司、佐賀洋介、川野邊哲代、永井義隆、富岡郁夫、関和彦
  • Organizer: 第40回 日本神経科学会
• [Presentation] 変異DNAJC13はエンドソーム輸送障害を介してαシヌクレイン神経毒性を増強する (2017)
  • Author(s): 長谷川隆文、吉田隼、鈴木マリ、菅野直人、小林潤平、福田光則、藤林明美、関口清俊、江面道典、菊池昭夫、武田篤、望月秀樹、永井義隆、青木正志
  • Organizer: 第40回 日本神経科学会
• [Presentation] 食餌制限は神経変性疾患モデルショウジョウバエの神経変性を改善する (2017)
  • Author(s): 鈴木マリ、Anne-Marie Neumann、齊藤勇二、藤掛伸宏、和田圭司、三五一憲、永井義隆
  • Organizer: 第27回 病態生理学会大会
• [Presentation] DNAJC13 mutation aggravates α SYN-induced neurotoxicity through alteration of endosomal trafficking. (2017)
  • Author(s): 吉田隼、長谷川隆文、鈴木マリ、菅野直人、小林潤平、福田光則、藤林明美、関口清俊、江面道典、菊池昭夫、武田篤、望月秀樹、永井義隆、青木正志
  • Organizer: 第11回 パーキンソン病・運動障害疾患コングレス
• [Presentation] 慢性的な中途覚醒の増加はアルツハイマー病モデルマウスのアミロイドβ病理を悪化させる (2017)
  • Author(s): 皆川栄子、宮崎歴、丸尾和司、八木原紘子、藤田寛美、和田圭司、永井義隆
  • Organizer: 第12回 臨床ストレス応答学会
• [Presentation] 中途覚醒の増加はアルツハイマー病モデルマウスのアミロイドβ病理を悪化させる (2017)
  • Author(s): 皆川栄子、宮崎歴、丸尾和司、八木原紘子、藤田寛美、和田圭司、永井義隆
  • Organizer: 第36回 日本認知症学会学術集会
• [Presentation] GBA機能喪失はα-シヌクレインの異常構造変化を促進して神経変性を悪化させる (2017)
  • Author(s): 鈴木マリ、藤掛伸宏、武内敏秀、香山(古金谷)綾子、中嶋和紀、平林義雄、和田圭司、三五一憲、永井義隆
  • Organizer: 第36回 日本認知症学会学術集会
• [Presentation] The search for genes that modulate FUS-mediated phenotypes by Drosophila amyotrophic lateral sclerosis model. (2017)
  • Author(s): 東裕美子、徳田隆彦、櫛村由紀恵、山本格、上岡伊吹、吉田英樹、水田依久子、上山盛夫、永井義隆、中川正法、水野 敏樹、山口政光
  • Organizer: 第40回 日本分子生物学会・第90回 日本生化学会
• [Presentation] ter94機能喪失変異はTBPHノックダウンによるALSショウジョウバエモデルの表現型を増悪する (2017)
  • Author(s): 櫛村由紀恵、徳田隆彦、東裕美子、山本格、上岡伊吹、水田依久子、水野 敏樹、中川正法、上山盛夫、永井義隆、吉田英樹、山口政光
  • Organizer: 第40回 日本分子生物学会・第90回 日本生化学会
• [Book] タンパク質のアモルファス凝集と溶解性―基礎研究からバイオ産業・創薬研究への応用まで－ (2019)
  • Author(s): 小澤大作、武内敏秀、永井義隆
  • Total Pages: 283
  • Publisher: シーエムシー出版
  • ISBN: 9784781313979
• [Book] パラダイムシフトをもたらすエクソソーム機能研究最前線 (2017)
  • Author(s): 落谷 孝広
  • Total Pages: 282
  • Publisher: エヌ・ティー・エス
  • ISBN: 9784860434656
• [Book] 動物／疾患モデルの作製技術・病態解析・評価手法 (2017)
  • Author(s): 永井 義隆 他
  • Total Pages: 428
  • Publisher: 技術情報協会
  • ISBN: 9784861046650
• [Remarks] 大阪大学大学院医学系研究科 神経難病認知症探索治療学寄附講座
  • URL: http://www2.med.osaka-u.ac.jp/neurother/