Regulation of PirB, a receptor causing neurodegenerative diseases

• Project/Area Number: 16K21268
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology; General pharmacology
• Research Institution: Yokohama City University
• Principal Investigator: KURIHARA Yuji 横浜市立大学, 生命医科学研究科, 特任助教 (00634552)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 神経科学 / 薬理学 / 神経疾患 / 受容体制御

Outline of Final Research Achievements

Paired immunoglobulin-like receptor B (PirB) is a novel functional receptor for oligomerized beta-amyloid impairing cognitive and memory function in Alzheimer’s disease. I examined the regulation of the molecular function of PirB bound by oligomerized beta-amyloid. I found that LOTUS interacts with PirB. Furthermore, overexpression of LOTUS with PirB in COS7 cells blocked the binding of oligomerized beta-amyloid to PirB. Moreover, an antibody against PirB also interfered with the binding of oligomerized beta-amyloid to PirB overexpressed in COS7 cells. These data suggest that LOTUS or the antibody might inhibit the physiological function of PirB induced by oligomerized beta-amyloid.

Research Products

• [Journal Article] Cerebrospinal fluid level of Nogo receptor 1 antagonist lateral olfactory tract usher substance (LOTUS) correlates inversely with the extent of neuroinflammation (2018)
  • Author(s): Takahashi Keita、Takeuchi Hideyuki、Kurihara Yuji、Doi Hiroshi、Kunii Misako、Tanaka Kenichi、Nakamura Haruko、Fukai Ryoko、Tomita-Katsumoto Atsuko、Tada Mikiko、Higashiyama Yuichi、Joki Hideto、Koyano Shigeru、Takei Kohtaro、Tanaka Fumiaki
  • Journal Title: Journal of Neuroinflammation Volume: 15 Issue: 1 Pages: 46-46
  • DOI: 10.1186/s12974-018-1084-x
  • Peer Reviewed / Open Access
• [Journal Article] The soluble form of LOTUS inhibits Nogo receptor-mediated signaling by interfering with the interaction between Nogo receptor type 1 and p75 neurotrophin receptor. (2018)
  • Author(s): Kawakami Y, Kurihara Y, Saito Y, Fujita Y, Yamashita T, Takei K.
  • Journal Title: J Neurosci. Volume: 38 Issue: 10 Pages: 2589-2604
  • DOI: 10.1523/jneurosci.0953-17.2018
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of lateral olfactory tract development by Nogo-A, Nogo receptor-1 and LOTUS proteins. (2017)
  • Author(s): Kurihara Y, Takei K.
  • Journal Title: Trends Dev Biol. Volume: 10 Pages: 41-47
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of axonal regeneration by the level of function of endogenous Nogo receptor antagonist LOTUS (2017)
  • Author(s): Hirokawa, T., Zou, Y., Kurihara, Y., Jiang, Z., Sakakibara, Y., Ito, H., Funakoshi, K., Kawahara, N., Goshima, Y., Strittmatter, S.M., and Takei, K.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 12119-12119
  • DOI: 10.1038/s41598-017-12449-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] LOTUS overexpression accelerates neuronal plasticity after focal brain ischemia in mice. (2017)
  • Author(s): Takase H, Kurihara Y, Yokoyama TA, Kawahara N, Takei K.
  • Journal Title: PLoS One Volume: 12 Issue: 9 Pages: e0184258-e0184258
  • DOI: 10.1371/journal.pone.0184258
  • Peer Reviewed / Open Access
• [Journal Article] Blockade of chondroitin sulfate proteoglycans-induced axonal growth inhibition by LOTUS (2017)
  • Author(s): Kurihara, Y., Saito, Y., and Takei, K.
  • Journal Title: Neuroscience Volume: 356 Pages: 265-274
  • DOI: 10.1016/j.neuroscience.2017.05.034
  • Peer Reviewed / Open Access
• [Journal Article] Axonal branching in lateral olfactory tract is promoted by Nogo signaling (2016)
  • Author(s): Iketani M, Yokoyama T, Kurihara Y, Strittmatter SM, Goshima Y, Kawahara N, Takei K
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 39586-39586
  • DOI: 10.1038/srep39586
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 神経回路形成因子LOTUSの軸索再生阻害因子PirBに対する拮抗作用. (2017)
  • Author(s): 栗原 裕司, 竹居 光太郎.
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎ブリックホール（長崎県）
  • Year and Date: 2017-03-17
• [Presentation] 神経回路形成因子LOTUSは神経突起伸長を促進する. (2017)
  • Author(s): 栗原 裕司, 川上 裕, 竹居 光太郎.
  • Organizer: 第60回日本神経化学会大会
• [Presentation] LOTUS, a neural circuit formation factor, blocks PirB-mediated axon growth inhibition. (2017)
  • Author(s): Kurihara Y, Takei K.
  • Organizer: The 26th Biennial Meeting of the International Society for Neurochemistry and the European Society for Neurochemistry
  • Int'l Joint Research
• [Presentation] LOTUSはNogoにより誘起されるPirBの軸索伸長阻害を抑制する. (2016)
  • Author(s): 栗原 裕司, 竹居 光太郎.
  • Organizer: 第59回日本神経化学会大会
  • Place of Presentation: 福岡国際会議場（福岡県）
  • Year and Date: 2016-09-08
• [Presentation] LOTUSはPirBのアンタゴニストとして機能する. (2016)
  • Author(s): 栗原 裕司, 竹居 光太郎.
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県）
  • Year and Date: 2016-07-20