Brain environment and neurodegeneration based on optineurin mutations

• Project Area: Brain Environment
• Project/Area Number: 23111008
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Hiroshima University
• Principal Investigator: Kawakami Hideshi 広島大学, 原爆放射線医科学研究所, 教授 (70253060)
• Co-Investigator(Kenkyū-buntansha): KATO HIDEMASA 愛媛大学, 大学院医学研究科, 准教授 (50292123)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥113,230,000 (Direct Cost: ¥87,100,000、Indirect Cost: ¥26,130,000); Fiscal Year 2015: ¥20,410,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥4,710,000); Fiscal Year 2014: ¥20,410,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥4,710,000); Fiscal Year 2013: ¥21,450,000 (Direct Cost: ¥16,500,000、Indirect Cost: ¥4,950,000); Fiscal Year 2012: ¥21,320,000 (Direct Cost: ¥16,400,000、Indirect Cost: ¥4,920,000); Fiscal Year 2011: ¥29,640,000 (Direct Cost: ¥22,800,000、Indirect Cost: ¥6,840,000)
• Keywords: 神経疾患 / モデル動物 / 脳、神経疾患 / 神経科学 / 筋萎縮性側索硬化症 / iPS細胞 / オプチニューリン

Outline of Final Research Achievements

To clarify the function of optineurin , which we found as a causative gene of amyotrophic lateral sclerosis, and to make the model mouse of amyotrophic lateral sclerosis, we made the optineurin knock-out mouse. We observed the behavior and body weight of the knock-out mouse, and we found no difference between the controls and the knock-out mouse.

Research Products

• [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] Multicenter Study of Intravenous Recombinant Tissue Plasminogen Activator Infusion around Hiroshima, Japan: The Hiroshima Acute Stroke Retrospective and Prospective Registry Study (2015)
  • Author(s): Aoki S, Hosomi N, Sueda Y, Kono T, Takamatsu K, Ohyama H, Torii T, Kitamura T, Nomura E, Noda K, Ohtsuki T, Matsumoto M, and the HARP Registry Study Group.
  • Journal Title: Journal of Stroke and Cerebrovascular Diseases Volume: 24 Issue: 12 Pages: 2747-2753
  • DOI: 10.1016/j.jstrokecerebrovasdis.2015.08.005
  • Peer Reviewed / Acknowledgement Compliant
• [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
• [Journal Article] Immunoreactivity of valosin-containing protein in sporadic amyotrophic lateral sclerosis and in a case of its novel mutant. (2014)
  • Author(s): Ayaki T
  • Journal Title: cta Neuropathol Commun Volume: 2 Pages: 172-172
  • 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] DYT6 in Japan-genetic screening and clinical characteristics of the patients. (2014)
  • Author(s): Miyamoto R, Koizumi H, Morino H, Kawarai T, Maruyama H, Mukai Y, Miyashiro A, Sako W, Izumi Y, Kawakami H, Kaji R.
  • Journal Title: Mov Disord. Volume: 29 Issue: 2 Pages: 278-280
  • DOI: 10.1002/mds.25745
  • Peer Reviewed
• [Journal Article] Exome sequencing reveals a novel MRE11 mutation in a patient with progressive myoclonic ataxia. (2014)
  • Author(s): Miyamoto R, Morino H, Yoshizawa A, Miyazaki Y, Maruyama H, Murakami N, Fukada K, Izumi Y, Matsuura S, Kaji R, Kawakami H.
  • Journal Title: J Neurol Sci. Volume: 337 Issue: 1-2 Pages: 219-223
  • DOI: 10.1016/j.jns.2013.11.032
  • Peer Reviewed
• [Journal Article] Exome sequencing reveals a novel ANO10 mutation in a Japanese patient with autosomal recessive spinocerebellar ataxia. (2014)
  • Author(s): Maruyama H, Morino H, Miyamoto R, Murakami N, Hamano T, Kawakami H.
  • Journal Title: Clin Genet. Volume: 85 Issue: 3 Pages: 296-297
  • DOI: 10.1111/cge.12140
  • Peer Reviewed
• [Journal Article] Oromandibular dystonia associated with SCA36. (2013)
  • Author(s): Miyashiro A, Sugihara K, Kawarai T, Miyamoto R, Izumi Y, Morino H, Maruyama H, Orlacchio A, Kawakami H, Kaji R.
  • Journal Title: Mov Disord. Volume: 28 Issue: 4 Pages: 558-559
  • DOI: 10.1002/mds.25304
  • Peer Reviewed
• [Journal Article] Optineurin suppression causes neuronal cell death via NF-κB pathway. (2013)
  • Author(s): Akizuki M, Yamashita H, Uemura K, Maruyama H, Kawakami H, Ito H, Takahashi R.
  • Journal Title: J Neurochem Volume: 126(6) Issue: 6 Pages: 2230-41
  • DOI: 10.1111/jnc.12326
  • Peer Reviewed / Open Access
• [Journal Article] An autopsy case of sporadic amyotrophic lateral sclerosis associated with the I113T SOD1 mutation. (2013)
  • Author(s): Nakamura S, Wate R, Kaneko S, Ito H, Oki M, Tsuge A, Nagashima M, Asayama S, Fujita K, Nakamura M, Maruyama H, Kawakami H, Kusaka H.
  • Journal Title: Neuropathology Volume: 34 Pages: 58-63
  • Peer Reviewed
• [Journal Article] Clinicopathologic features of autosomal recessive amyotrophic lateral sclerosis associated with optineurin mutation. (2013)
  • Author(s): Kamada M, Izumi Y, Ayaki T, Nakamura M, Kagawa S, Kudo E, Sako W, Maruyama H, Nishida Y, Kawakami H, Ito H, Kaji R.
  • Journal Title: Neuropathology Volume: 34 Issue: 1 Pages: 64-70
  • DOI: 10.1111/neup.12051
  • Peer Reviewed
• [Journal Article] Optineurin and amyotrophic lateral sclerosis (2013)
  • Author(s): Maruyama H, Kawakami H
  • Journal Title: Geriatr Gerontol Int Volume: 13(3) Issue: 3 Pages: 528-32
  • DOI: 10.1111/ggi.12022
  • Peer Reviewed
• [Journal Article] Convenient diagnosis of spinal and bulbar muscular atrophy using a microchip electrophoresis system. (2013)
  • Author(s): Hirofumi Maruyama
  • Journal Title: Am J Neurodegener Dis. Volume: 2 Pages: 35-9
  • Peer Reviewed
• [Journal Article] Severe brain atrophy after long-term survival seen in siblings with familial amyotrophic lateral sclerosis and a mutation in the optineurin gene : a case series (2012)
  • Author(s): Ueno H, Kobatake K, Matsumoto M, Morino H, Maruyama H, Kawakami H
  • Journal Title: J Med Case Reports Volume: 5 Issue: 1 Pages: 573-573
  • DOI: 10.1186/1752-1947-5-573
  • Peer Reviewed
• [Journal Article] Optineurin with amyotrophic lateral sclerosis-related mutations abrogates inhibition of interferon regulatory factor-3 activation (2011)
  • Author(s): Sakaguchi T, Irie T, Kawabata R, Yoshida A, Maruyama H, Kawakami H
  • Journal Title: Neuroscience Letters Volume: 505 Issue: 3 Pages: 279-281
  • DOI: 10.1016/j.neulet.2011.10.040
  • NAID: 120005308229
  • Peer Reviewed
• [Presentation] MAPTの新規挿入変異を認めたFTDP17の2家系 (2014)
  • Author(s): 森野豊之
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡市
  • Year and Date: 2014-05-20 – 2014-05-23
• [Presentation] Exome sequence identifies a novel MRE11 mutation in a patient with generalized myoclonic tremor. (2012)
  • Author(s): Ryosuke Miyamoto
  • Organizer: 62nd Annual Meeting of The American Society of Human Genetics
  • Place of Presentation: San Francisco, アメリカ合衆国
  • Year and Date: 2012-11-06
• [Presentation] 筋萎縮性側索硬化症の新規原因遺伝子optineurinの同定 (2012)
  • Author(s): 1.丸山博文
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2012-05-22
  • Invited
• [Presentation] ALS関連遺伝子のスクリーニング (2012)
  • Author(s): 3. 杉原勝宣
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2012-05-22
• [Presentation] Perrault症候群の新規原因遺伝子
  • Author(s): 森野豊之、宮本亮介、丸山博文、川上秀史
  • Organizer: 第54回日本神経学術大会
  • Place of Presentation: 東京