Establishing the basic study for unmyelinated and myelinated central nervous system

• Project/Area Number: 24659436
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: NUKINA Nobuyuki 独立行政法人理化学研究所, 脳科学総合研究センター, 客員主管研究員 (10134595)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 無髄線維 / 線条体投射線維 / sodium channel / beta4 subunit / Nav1.2 / ナトリウムチャンネル / 線条体中型有棘細胞 / 線条体 / 無髄神経

Outline of Final Research Achievements

The role of unmyelinated fiber in central nervous system is not well elucidated. Even which nervous system is unmylinated is well unknown. We recently found the striatal projection fibers are unmylinated suggested by the distribution pattern of sodium channel beta4 subunit. In this study we further confirm this fact and identified several features of those unmyelinated fibers(Miyazaki et al Nat Commun2014)

Research Products

• [Journal Article] Sodium channel β1 subunit localizes to axon initial segments of excitatory and inhibitory neurons and shows regional heterogeneity in mouse brain. (2015)
  • Author(s): Wimmer VC, Harty RC, Richards KL, Phillips AM, Miyazaki H, Nukina N, Petrou S.
  • Journal Title: J Comp Neurol. Volume: 523 Issue: 5 Pages: 814-30
  • DOI: 10.1002/cne.23715
  • Peer Reviewed
• [Journal Article] Singular localization of sodium channel β4 subunit in unmyelinated fibres and its role in the striatum. (2014)
  • Author(s): Miyazaki H, Oyama F, Inoue R, Aosaki T, Abe T, Kiyonari H, Kino Y, Kurosawa M, Shimizu J, Ogiwara I, Yamakawa K, Koshimizu Y, Fujiyama F, Kaneko T, Shimizu H, Nagatomo K, Yamada K, Shimogori T, Hattori N, Miura M, Nukina N.
  • Journal Title: Nat Commun. Volume: 5 Issue: 1 Pages: 5525-5525
  • DOI: 10.1038/ncomms6525
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] NF-Y inactivation causes atypical neurodegeneration characterized by ubiquitin and p62 accumulation and endoplasmic reticulum disorganization (2014)
  • Author(s): Yamanaka, T., Tosaki, A., Kurosawa, M., Matsumoto, G., Koike, M., Uchiyama, Y., Maity, S.N., Shimogori, T., Hattori, N. & Nukina, N.
  • Journal Title: Nat. Commun. Volume: 5 Issue: 1 Pages: 3354-3354
  • DOI: 10.1038/ncomms4354
  • Peer Reviewed
• [Journal Article] Cyclin-dependent kinase 5 phosphorylates and induces the degradation of ataxin-2 (2014)
  • Author(s): Asada, A., Yamazaki, R., Kino, Y., Saito, T., Kimura, T., Miyake, M., Hasegawa, M., Nukina, N. & Hisanaga, S.
  • Journal Title: Neurosci. Lett. Volume: 563 Pages: 112-117
  • DOI: 10.1016/j.neulet.2014.01.046
  • Peer Reviewed
• [Journal Article] Dexamethasone induces heat shock response and slows down disease progression in mouse and fly models of Huntington's disease (2014)
  • Author(s): Maheshwari, M., Bhutani, S., Das, A., Mukherjee, R., Sharma, A., Kino, Y., Nukina, N. & Jana, N.R.
  • Journal Title: Hum. Mol. Genet. Volume: 23 Issue: 10 Pages: 2737-2751
  • DOI: 10.1093/hmg/ddt667
  • Peer Reviewed
• [Journal Article] Intranuclear aggregation of mutant FUS/TLS as a molecular pathomechanism of amyotrophic lateral sclerosis (2014)
  • Author(s): Nomura, T., Watanabe, S., Kaneko, K., Yamanaka, K., Nukina, N. & Furukawa, Y.
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 2 Pages: 1192-1202
  • DOI: 10.1074/jbc.m113.516492
  • Peer Reviewed / Open Access
• [Journal Article] Loss of aPKClambda in differentiated neurons disrupts the polarity complex but does not induce obvious neuronal loss or disorientation in mouse brains (2013)
  • Author(s): Yamanaka, T., Tosaki, A., Kurosawa, M., Akimoto, K., Hirose, T., Ohno, S., Hattori, N. & Nukina, N.
  • Journal Title: PloS one Volume: 8 Issue: 12 Pages: e84036-e84036
  • DOI: 10.1371/journal.pone.0084036
  • Peer Reviewed / Open Access
• [Journal Article] Intracellular seeded aggregation of mutant Cu,Zn-superoxide dismutase associated with amyotrophic lateral sclerosis (2013)
  • Author(s): Furukawa, Y., Kaneko, K., Watanabe, S., Yamanaka, K. & Nukina, N.
  • Journal Title: FEBS Lett. Volume: 587 Issue: 16 Pages: 2500-2505
  • DOI: 10.1016/j.febslet.2013.06.046
  • Peer Reviewed / Open Access
• [Journal Article] Functional diversity of protein fibrillar aggregates from physiology to RNA granules to neurodegenerative diseases (2013)
  • Author(s): Furukawa, Y. & Nukina, N.
  • Journal Title: Biochim. Biophys. Acta Volume: 1832 Issue: 8 Pages: 1271-1278
  • DOI: 10.1016/j.bbadis.2013.04.011
  • Peer Reviewed
• [Journal Article] Modulation of voltage-gated K+ channels by the sodium channel beta1 subunit (2012)
  • Author(s): Nguyen, H.M.
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 109 Issue: 45 Pages: 18577-18582
  • DOI: 10.1073/pnas.1209142109
  • Peer Reviewed
• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (2012)
  • Author(s): Klionsky, D. J.
  • Journal Title: Autophagy Volume: 8 Pages: 445-544
  • Peer Reviewed
• [Journal Article] ROCK-phosphorylated vimentin modifies mutant huntingtin aggregation via sequestration of IRBIT (2012)
  • Author(s): Bauer PO
  • Journal Title: Molecular Neurodegeneration Volume: 7(1) Issue: 1 Pages: 43-43
  • DOI: 10.1186/1750-1326-7-43
  • Peer Reviewed
• [Journal Article] Post-aggregation oxidation of mutant huntingtin controls the interactions between aggregates (2012)
  • Author(s): Mitomi, Y.
  • Journal Title: Journal of Biological Chemistry Volume: 287 Issue: 41 Pages: 34764-34775
  • DOI: 10.1074/jbc.m112.387035
  • Peer Reviewed
• [Journal Article] Local unfolding of Cu, Zn superoxide dismutase monomer determines the morphology of fibrillar aggregates (2012)
  • Author(s): Ding, F.
  • Journal Title: Journal of Molecular Biology Volume: 421 Issue: 4-5 Pages: 548-560
  • DOI: 10.1016/j.jmb.2011.12.029
  • Peer Reviewed
• [Presentation] The pathomechanism of Huntington disease:factors related to its pathological cascades（ハンチントン病の分子病態） (2015)
  • Author(s): Nukina, N.
  • Organizer: 第１２０回日本解剖学会・第９２回日本生理学会大会合同大会
  • Place of Presentation: 神戸国際会議場（神戸ポートアイランド）
  • Year and Date: 2015-03-21 – 2015-03-23
  • Invited
• [Presentation] Autophagic machinery for degrading the misfolded proteins (2012)
  • Author(s): Nukina, N.
  • Organizer: The 6th International Symposium of Autophagy 2012
  • Place of Presentation: Nago, Japan
  • Invited
• [Presentation] Role of NF-Y transcription factor in neuronal cell maintenance and chaperone gene expression (2012)
  • Author(s): Yamanaka, T.
  • Organizer: MBO | EMBL Symposia 2012: Quality Control - From Molecules to Organelles
  • Place of Presentation: Heiderberg, Germany
• [Remarks] 大脳における抑制性の無髄神経線維束の発見
  • URL: http://www.juntendo.ac.jp/graduate/pdf/news13.pdf