Development of pathological mechanism and therapy for amyotrophic lateral sclerosis using optineurin mice

• Project/Area Number: 26293211
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Hiroshima University
• Principal Investigator: Maruyama Hirofumi 広島大学, 医歯薬保健学研究院, 教授 (90304443)
• Co-Investigator(Kenkyū-buntansha): 川上 秀史 広島大学, 原爆放射線医科学研究所, 教授 (70253060)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: 筋萎縮性側索硬化症 / オプチニューリン / ノックアウトマウス / 脳神経疾患 / 神経分子病態学 / モデルマウス

Outline of Final Research Achievements

We generated optineurin (OPTN) knockout (KO) mice. Compared to wild-type mice, 24-month-old OPTN-KO mice did not differ for survival curve, body weight or motor function. Inclusion body like structures were observed in the cell bodies of motor neurons in the lumbar spinal cord. Golgi fragmentation was increased. Axonal degeneration was observed in sciatic nerve.
Double modification mice of SOD1 and OPTN showed elongation of life time.

Research Products

• [Journal Article] The origins of rimmed vacuoles and granulovascuolar degeneration bodies are similar and are associated with the Wnt signaling pathway (2017)
  • Author(s): Yukari Murata-Shinozaki, Tetsuya Takahashi, Tomoyasu Matsubara, Hirofumi Maruyama, Yuishin Izumi, Masayasu Matsumoto
  • Journal Title: Neuroscience Letters Volume: 638 Pages: 55-59
  • DOI: 10.1016/j.neulet.2016.12.014
  • Peer Reviewed
• [Journal Article] Sex differences in variances of multi-channel surface electromyography distribution of the vastus lateralis muscle during isometric knee extension in young adults (2017)
  • Author(s): Yuichi Nishikawa, Kohei Watanebe, Tetsuya Takahashi, Noahisa Hosomi, Naoya Orita, Yukio Mikami, Hirofumi Maruyama, Hiroaki Kimura, Masayasu Matsumoto
  • Journal Title: European Journal of Applied Physiology Volume: 117 Issue: 3 Pages: 583-589
  • DOI: 10.1007/s00421-017-3559-3
  • Peer Reviewed
• [Journal Article] Pyrimethamine-indeuced transient leukoencephalopathy: similarity to methotrexate encephalopathy (2017)
  • Author(s): Hiroki Ueno, Hidetada Yamada, Naoyuki Hara, Ayako Miyoshi, Hirofumi Maruyama
  • Journal Title: Neurology and Clinical Neuroscience Volume: 2 Issue: 2 Pages: 75-75
  • DOI: 10.1111/ncn3.12111
  • Peer Reviewed
• [Journal Article] Maximum tongue pressure is associated with swallowing dysfunction in ALS patients (2017)
  • Author(s): Aya Hiraoka, Mineka Yoshikawa, Masahiro Nakamori, Naohisa Hosomi, Toshikazu Nagasaki, Takahiro Mori, Masaya Oda, Hirofumi Maruyama, Mitsuyoshi Yoshida, Yuishin Izumi, Masayasu Matsumoto, Kazuhiro Tsuga
  • Journal Title: Dysphagia Volume: 印刷中 Issue: 4 Pages: 542-547
  • DOI: 10.1007/s00455-017-9797-z
  • Peer Reviewed / Open Access
• [Journal Article] Translocated in liposarcoma regulates the ditrubution and funciton of mammalian enabled, a modulator of actin dynamics (2016)
  • Author(s): Sugiura T, Matsuda S, Kurosaka S, Nakai N, Fukumoto K, Takahashi T, Maruyama H, Imaizumi K, Matsumoto M, Takumi T
  • Journal Title: FEBS J Volume: 283 Issue: 8 Pages: 1475-1487
  • DOI: 10.1111/febs.13685
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The multidisciplinary swallowing team approach decreases pneumonia onset in acute stroke patients. (2016)
  • Author(s): Shiro Aoki, Naohisa Hosomi, Junko Hirayama, Masahiro Nakamori, Mineka Yoshikawa, Tomohisa Nezu, Satoshi Kubo, Yuka Nagano, Akiko Nagao, Naoya Yamane, Yuichi Nishikawa, Megumi Takamoto, Hiroki Ueno, Kazuhide Ochi, Hirofumi Maruyama, Hiromi Yamamoto, Masayasu Matsumoto
  • Journal Title: PLoS One Volume: 11 Issue: 5 Pages: e0154608-e0154608
  • DOI: 10.1371/journal.pone.0154608
  • Peer Reviewed / Open Access
• [Journal Article] Temporal Trends in Stroke Severity and Prior Antithrombotic Use Among Acute Ischemic Stroke Patients in Japan (2016)
  • Author(s): Tomohisa Nezu, Naohisa Hosomi, Gregory YH Lip, Shiro Aoki, Ryo Shimomura, Hirofumi Maruyama, Yoshiki Yagita, Masayasu Matsumoto, Shotai Kobayashi, The Japan Standard Stroke Registry Study Group
  • Journal Title: Circulation Journal Volume: 80 Issue: 9 Pages: 2033-2036
  • DOI: 10.1253/circj.CJ-16-0374
  • NAID: 130005406874
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Deviation in the recovery of the lower limb and respiratory muscles of patients with polymyositis: a preliminary clinical study (2016)
  • Author(s): Yuichi Nishikawa, Naohisa Hosomi, Hiroyuki Ueno, Takeshi Kurashige, Kazuhide Ochi, Tetsuya Takahashi, Naoya Orita, Kazuyuki Ueda, Hirofumi Maruyama, Hiroaki Kimura, Masayasu Matsumoto
  • Journal Title: Journal of Physical Therapy Science Volume: 28 Issue: 9 Pages: 2652-2655
  • DOI: 10.1589/jpts.28.2652
  • NAID: 130005265088
  • ISSN: 0915-5287, 2187-5626
  • Peer Reviewed
• [Journal Article] Warfarin-resistant deep vein thromnosis during the treatment of acute ischemic stroke in lung adenocarcinoma (2016)
  • Author(s): Hiroyuki Naito, Shiro Aoki, Naoko Sumi, Kazuhide Ochi, Naohisa Hosomi, Hirofumi Maruyama, Masayasu Matsumoto
  • Journal Title: Journal of Stroke and Cerebrovascular Diseases Volume: 25 Issue: 9 Pages: e141-e145
  • DOI: 10.1016/j.jstrokecerebrovasdis.2016.04.026
  • Peer Reviewed
• [Journal Article] Prediction of pneumonia in acute stroke patients using tongue pressure measurements (2016)
  • Author(s): Masahiro Nakamori, Naohisa Hosomi, Kenichi Ishikawa, Eiji Imamura, Takeo Shishido, Tomohiko Ohshita, Mineka Yoshikawa, Kazuhiro Tsuga, Shinichi Wakabayashi, Hirofumi Maruyama, Masayasu Matsumoto
  • Journal Title: PLOS ONE Volume: 11 Issue: 11 Pages: e0165837-e0165837
  • DOI: 10.1371/journal.pone.0165837
  • Peer Reviewed / Open Access
• [Journal Article] The identification of raft-derived tau-associated vesicles that are incorporated into immature tangles and paired helical filaments (2016)
  • Author(s): T Nishikawa, T Takahashi, M Nakamori, N Hosomi, H Maruyama, Y Miyazaki, Y Izumi, M Matsumoto
  • Journal Title: Neuropathology and Applied Neurobiology Volume: 42 Issue: 7 Pages: 639-653
  • DOI: 10.1111/nan.12288
  • Peer Reviewed
• [Journal Article] A Multidisciplinary Pain, Agitation, and Delirium Management Team Can Promote Rehabilitation in the Intensive Care Unit: A Case Report (2016)
  • Author(s): Yuichi Nishikawa, Shunsuke Taito, Kazuhiro Sarada, Kohei Ota, Yuko Tanabe, Naohisa Hosomi, Tetsuya Takahashi, Hirofumi Maruyama, Hiroaki Kimura, Masayasu Matsumoto
  • Journal Title: Progress in Rehabilitation Medicine Volume: 1 Issue: 0 Pages: n/a
  • DOI: 10.2490/prm.20160010
  • NAID: 130005252929
  • ISSN: 2432-1354
  • Peer Reviewed
• [Journal Article] Tongue thickness evaluation using ultrasonography can predict swallowing function in amyotrophic lateral sclerosis patients (2016)
  • Author(s): Masahiro Nakamori, Naohisa Hosomi, Sachiko Takaki, Masaya Oda, Aya Hiraoka, Mineka Yoshikawa, Hayato Matsushima, Kazuhide Ochi, Kazuhiro Tsuga, Hirofumi Maruyama, Yuishin Izumi, Masayasu Matsumoto
  • Journal Title: Clinical Neurophysiology Volume: 127 Issue: 2 Pages: 1669-1674
  • DOI: 10.1016/j.clinph.2015.07.032
  • Peer Reviewed
• [Journal Article] Endothelial dysfunction is associated with the severity of cerebral small vessel disease. (2015)
  • Author(s): Nezu T, Hosomi N, Aoki S, Sugimoto T, Kubo S, Araki M, Matsushima H, Mukai T, Takahashi T, Maruyama H, Higashi Y, Matsumoto M.
  • Journal Title: Hyperten Res. Volume: 38 Issue: 4 Pages: 291-297
  • DOI: 10.1038/hr.2015.4
  • Peer Reviewed
• [Journal Article] Telomere G-tail Length is a Promising Biomarker Related to White Matter Lesions and Endothelial Dysfunction in Patients With Cardiovascular Risk: A Cross-sectional Study. (2015)
  • Author(s): Nezu T, Hosomi N, Takahashi T, Anno K, Aoki S, Shimamoto A, Maruyama H, Hayashi T, Matsumoto M, Tahara H.
  • Journal Title: EBioMedicine. Volume: 2(8) Issue: 8 Pages: 958-65
  • DOI: 10.1016/j.ebiom.2015.05.025
  • NAID: 120006796554
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Japan Statin Treatment against Recurrent Stroke (J-STARS): a multicenter, randomized, open-label, parallel-group study (2015)
  • Author(s): N Hosomi, Y Nagai, T Kohriyama, T Ohtsuki, S Aoki, T Nezu, Hirofumi Maruyama, N Sunami, C Yokota, K Kitagawa, Y Terayama, M Takagi, S Ibayashi, M Nakamura, H Origasa, M Fukushima, E Mori, K Minematsu, S Uchiyama, Y Shinohara, T Yamaguchi, M Matsumoto
  • Journal Title: EBioMedicine Volume: 2 Issue: 9 Pages: 1071-1078
  • DOI: 10.1016/j.ebiom.2015.08.006
  • NAID: 120006796553
  • Peer Reviewed
• [Journal Article] Immediate effect of passive and active stretching on hamstrings flexibility: a single-blinded randomized control trial (2015)
  • Author(s): Yuichi Nishikawa, Jyunya Aizawa, Naohiko Kanemura, Tetsuya Takahashi, Naohisa Hosomi, Hirofumi Maruyama, Hiroaki Kimura, Masayasu Matsumoto, Kiyomi Takayanagi
  • Journal Title: Journal of Physical Therapy Science Volume: 27 Issue: 10 Pages: 3167-3170
  • DOI: 10.1589/jpts.27.3167
  • NAID: 130005105943
  • ISSN: 0915-5287, 2187-5626
  • Peer Reviewed
• [Journal Article] A case of recurrent ischemic stroke involving sub-acute progressive intracranial cerebral arterial sclerosis prior to diagnosis with JAK2-mutated polycythemia vera (2015)
  • Author(s): Tomohisa Nezu, Shiro Aoki, Kazuhide Ochi, Sayaka Sugihara, Tetsuya Takahashi, Naohisa Hosomi, Hirofumi Maruyama, Masayasu Matsumoto
  • Journal Title: Journal of Stroke and Cerebrovascular Disease Volume: 24 Issue: 12 Pages: e4-e6
  • DOI: 10.1016/j.jstrokecerebrovasdis.2015.08.040
  • Peer Reviewed
• [Journal Article] A mutation in the low voltage -gated calcium channel CACNA1G alters the physiological properties of the channel, causing spinocerebellar ataxia. (2015)
  • Author(s): Morino H., Matsuda Y., Muguruma K., Miyamoto R., Ohsawa R., Ohtake T., Otobe R., Watanabe M., Maruyama H., Hashimoto K., Kawakami H.
  • Journal Title: Molecular Brain Volume: 8 Issue: 1 Pages: 1-9
  • DOI: 10.1186/s13041-015-0180-4
  • Peer Reviewed / Open Access
• [Journal Article] EAuthor’s reply to Drs M van Blitterswijk, R Rademakers and LH van den Berg (2014)
  • Author(s): Taku Homma, Utako Nagaoka, Akihiro Kawata, Yoko Mochizuki, Hideshi Kawakami, Hirofumi Maruyama, Shiro Matsubara, Takashi Komori
  • Journal Title: Neuropathology and Applied Neurobiology Volume: 40 Issue: 3 Pages: 359-360
  • DOI: 10.1111/nan.12105
  • Peer Reviewed / Open Access
• [Journal Article] Detecting gene mutations in Japanese Alzheimer's patients by semiconductor sequencing. (2014)
  • Author(s): Yagi R
  • Journal Title: Neurobiol Aging Volume: 35 Issue: 7 Pages: 1780.e1-1780.e5
  • DOI: 10.1016/j.neurobiolaging.2014.01.023
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Paroxysmal dysarthria and ataxia in chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (2014)
  • Author(s): Hiroki Ueno, Hikaru Tomimura, Takeshi Yoshimoto, Kazuhide Ochi, Eiichi Nomura, Hirofumi Maruyama, Masayasu Matsumoto
  • Journal Title: Neurology and Clinical Neuroscience Volume: 2 Issue: 1 Pages: 13-15
  • DOI: 10.1111/ncn3.69
  • Peer Reviewed
• [Journal Article] A Japanese patient with familial ALS and a p.K510M mutation in the gene for FUS (FUS) resulting in the totally locked-in state (2014)
  • Author(s): Mochizuki Y, Kawata A, Maruyama H, Homma T, Watabe K, Kawakami H, Komori T, Mizutani T, Matsubara S
  • Journal Title: Neuropathology Volume: 34 Issue: 5 Pages: 504-509
  • DOI: 10.1111/neup.12130
  • Peer Reviewed
• [Journal Article] Mutations in Twinkle primase-helicase cause Perrault syndrome with neurologic features. (2014)
  • Author(s): Morino H
  • Journal Title: Neurology Volume: 83 Issue: 22 Pages: 2054-2061
  • DOI: 10.1212/wnl.0000000000001036
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 筋萎縮性側索硬化症患者における舌エコー、舌圧測定、嚥下造影検査での嚥下障害の検討 (2016)
  • Author(s): 中森正博、和泉唯信、織田雅也、平岡綾、吉川峰加、細見直永、丸山博文、松本昌泰
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸
• [Presentation] 人工呼吸管理下の筋萎縮性側索硬化症患者における深部静脈血栓症の検討 (2016)
  • Author(s): 福塲浩正、大森啓充、山崎雅美、丸山博文、宮地隆史、松本昌泰
  • Organizer: 第36回日本静脈学会総会
  • Place of Presentation: 弘前
• [Presentation] Serum and muscular KL-6/MUC1 are useful biomarker for GNE-myopathy (2015)
  • Author(s): T Kurashige, T Takahashi, Y Nagano, K Sugie, H Maruyama, S Ueno, M Matsumoto
  • Organizer: 22nd World Congress of Neurology
  • Place of Presentation: Santiago（チリ）
  • Year and Date: 2015-11-04
  • Int'l Joint Research
• [Presentation] Rimmed vaculores are positive for RIPK1 and RIPK3 (2015)
  • Author(s): T Kurashige, H Morino, Y Nagano, H Maruyama, M Matsumoto
  • Organizer: 20th International Congress of World Muscle Society
  • Place of Presentation: Brighton（英国）
  • Year and Date: 2015-10-01
  • Int'l Joint Research
• [Presentation] 次世代シーケンサを用いた筋萎縮性側索硬化症の原因遺伝子スクリーニング (2015)
  • Author(s): 森野豊之、松田由喜子、和泉唯信、丸山博文、川上秀史
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-23
• [Presentation] 人工呼吸器管理下の筋萎縮性側索硬化症患者における気道内圧の経時変化 (2015)
  • Author(s): 神原智美、竹田育子、山崎雅美、上利美智子、福場浩正、宮地隆史、丸山博文、松本昌泰
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-22
• [Presentation] 血清KL-6はGNE-myopathyの補助診断マーカーになり得る (2015)
  • Author(s): 倉重毅志、高橋哲也、永野義人、上利大、山脇健盛、時信弘、丸山博文、松本昌泰
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-22
• [Presentation] 3- and 4-repeat tau is phosphorylated and cleaved by transient cerebral ischemia (2015)
  • Author(s): 藤井裕樹、高橋哲也、向井智哉、田中茂、細見直永、丸山博文、酒井規雄、松本昌泰
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-20
• [Presentation] Perrault症候群の原因遺伝子C10orf2の変異によるmtDNA維持機構の障害 (2014)
  • Author(s): 森野豊之、松田由喜子、SB Pierce、平木啓子、丸山博文、MC King、川上秀史
  • Organizer: 日本人類遺伝学会第59回大会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-20
• [Presentation] A novel insertion mutation of MAPT causes FTDP-17 with distinct pathology. (2014)
  • Author(s): H Morino, Y Matsuda, R Ohsawa, K Hiraki, T Kurashige, Y Izumi, Y Yamazaki, T Takahashi, A Takashima, Y Soeda, T Miyasaka, H Higuchi, N Sahara, T Suhara, H Shimada, H Maruyama, H Ito, H Kawakami
  • Organizer: American Society of Human Genetics 64th Annual Meeting
  • Place of Presentation: San Diego（USA）
  • Year and Date: 2014-10-20
• [Presentation] KL-6/MUC1 is a novel diagnostic marker for GNE-myopathy (2014)
  • Author(s): T Kurashige, T Takahashi, Y Nagano, K Sugie, C Watanabe, H Maruyama, S Ueno, M Matsumoto
  • Organizer: 19th International Congress of the World Mauscle Society
  • Place of Presentation: Berlin（ドイツ）
  • Year and Date: 2014-10-08
• [Presentation] Endothilial dysfunction is associated with the severity of white matter lesions in patients with chronic cerebrovascular disease and comorbidity (2014)
  • Author(s): Tomohisa Nezu, Naohisa Hosomi, Shiro Aoki, Satoshi Kubo, Mutsuko Araki, Hayato Matsushima, Tomoya Mukai, Testuya Takahashi, Hirofumi Maruyama, Masayasu Matsumoto
  • Organizer: Asia Pacific Stroke Conference 2014
  • Place of Presentation: Taipei（台湾）
  • Year and Date: 2014-09-14
• [Presentation] FUS R521C変異を伴った家族性筋萎縮性側索硬化症の１剖検例 (2014)
  • Author(s): 望月葉子、川田明広、丸山博文、川上秀史、小森隆司、中野今治
  • Organizer: 第55回日本神経病理総会学術研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-06-06
• [Presentation] SOD1遺伝子L126S変異を伴う家族性筋萎縮性側索硬化症(FALS)の母娘例 (2014)
  • Author(s): 林健太郎、本間琢、望月葉子、長尾雅裕、川田明広、小森隆司、川上秀史、丸山博文、中野今治
  • Organizer: 第55回日本神経病理総会学術研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-06-06
• [Presentation] 全国在宅人工呼吸器装着者数調査2013 (2014)
  • Author(s): 宮地隆史、溝口功一、丸山博文、西澤正豊、松本昌泰
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-24
• [Presentation] MAPTの新規挿入変異を認めたFTDP-17の２家系 (2014)
  • Author(s): 森野豊之、平木啓子、倉重毅志、和泉唯信、山崎雄、高橋哲也、丸山博文、伊東秀文、川上秀史
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-21
• [Presentation] NF-κB経路を介したOptineurinのノックダウンによる神経細胞死 (2014)
  • Author(s): 秋月真由美、山下博史、植村健吾、丸山博文、川上秀史、伊東秀文、高橋良輔
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-21
• [Book] 神経内科看護の知識と実際 (2015)
  • Author(s): 丸山博文、松本昌泰
  • Publisher: メディカ出版