The molecular mechanism of the prion protein and the homolog which cause the neuro-degenerative/-protective function.

2010 Fiscal Year Final Research Report

• Project/Area Number: 20500324
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Nagasaki University
• Principal Investigator: YAMAGUCHI Naohiro Nagasaki University, 病院, 医員 (40432976)
• Co-Investigator(Kenkyū-buntansha): UEZONO YASUHITO 国立がんセンター研究所, がん患者病態生理研究部, 部長 (20213340)
• Project Period (FY): 2008 – 2010
• Keywords: 神経変性疾患 / プリオン

Research Abstract

In this study, We proved that the Prion protein(PrP) bind to the glutaminic acid receptor type I (mGluR1) which regulated the Ca2+ in nerve cells. So the function of PrP is to regulate the Ca2+ in the cell by interacting with mGluR1 receptor, and this suggests that neuronal degeneration is caused by the adjustment this mechanism's failure. The Purkinje cell death in the PrP knockout mouse (Ngsk Prnp-/-) and the neurodegeneration of prion disease might be caused by this mechanism. In addition, We cloned a new PrP intracting gene : plasmalemma vesicle associated protein (Plvap/PV-1) by expression cloning method using the cDNA library from mouse brain. Additionally we proved that Dpl which is homolog of PrP isn't influenced prion infection, and Shadoo which is another homolog of PrP may promote accumulation of PrPSc(abnormal type of Prion protein) in culture cell systems.

Research Products

• [Journal Article] Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion. (2011)
  • Author(s): Atarashi R, Satoh K, Sano K, Fuse T, Yamaguchi N, Ishibashi D, Matsubara T, Nakagaki T, Yamanaka H, Shirabe S, Yamada M, Mizusawa H, Kitamoto T, Klug G, McGlade A, Collins SJ, Nishida N.
  • Journal Title: Nat Med. 17(2) Pages: 175-178
  • Peer Reviewed
• [Journal Article] Human Papillomavirus DNA in Plasma of Patients with HPV16 DNA-positive Uterine Cervical Cancer. (2010)
  • Author(s): Shimada T, Yamaguchi N, Nishida N, Yamasaki K, Miura K, Katamine S, Masuzaki H.
  • Journal Title: Jpn J Clin Oncol.
  • Peer Reviewed
• [Journal Article] Escherichia coli contamination of menstrual blood and effect of bacterial endotoxin on endometriosis. (2010)
  • Author(s): Khan KN, Kitajima M, Hiraki K, Yamaguchi N, Katamine S, Matsuyama T, Nakashima M, Fujishita A, Ishimaru T, Masuzaki H.
  • Journal Title: Fertil Steril. 94(7) Pages: 2860-2863.e1-3
  • Peer Reviewed
• [Journal Article] case of unilateral adrenal hyperplasia being difficult to distinguish from aldosterone-producing adenoma. (2009)
  • Author(s): Shigematsu K, Yamaguchi N, Nakagaki T, Sakai H.
  • Journal Title: Exp Clin Endocrinol Diabetes. 117(3) Pages: 124-128
  • Peer Reviewed
• [Journal Article] A case of unilateral adrenal hyperplasia being difficult to distinguish from aldosterone-producing adenoma. (2009)
  • Author(s): Shigematsu K, Yamaguchi N, Nakagaki T, Sakai H.
  • Journal Title: Exp Clin Endocrinol Diabetes. 117(3) Pages: 124-128
  • Peer Reviewed
• [Journal Article] Bone marrow stroma cells are susceptible to prion infection. (2008)
  • Author(s): Takakura Y, Yamaguchi N, Nakagaki T, Satoh K, Kira J, Nishida N.
  • Journal Title: Biochem Biophys Res Commun. 377(3) Pages: 957-961
  • Peer Reviewed
• [Journal Article] Dominant-negative effects of the N-terminal half of prion protein on neurotoxicity of prion protein-like protein/doppel in mice. (2008)
  • Author(s): Yoshikawa D, Yamaguchi N, Ishibashi D, Yamanaka H, Okimura N, Yamaguchi Y, Mori T, Miyata H, Shigematsu K, Katamine S, Sakaguchi S.
  • Journal Title: J Biol Chem. 283(35) Pages: 24202-24211
  • Peer Reviewed
• [Journal Article] Analysis of mRNA expression for steroidogenic enzymes in the remaining adrenal cortices attached to adrenocortical adenomas. (2008)
  • Author(s): Shigematsu K, Nakagaki T, Yamaguchi N, Kawai K, Sakai H, Takahara O.
  • Journal Title: Eur J Endocrinol. 158(6) Pages: 867-878
  • Peer Reviewed
• [Presentation] Cellular prion protein regulates the intracellular Ca2+ signaling through its binding to metabotropic glutamate receptor type I, mGluR1. (2010)
  • Author(s): 松原岳大
  • Organizer: 第33回日本分子生物学会総会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-07
• [Presentation] Cellular prion protein binds to metabotropic glutamate receptor type I and regulates its function (2009)
  • Author(s): 松原岳
  • Organizer: 第32回日本分子生物学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-09
• [Presentation] 異常型プリオン蛋白質による神経細胞変性死におけるmGluR1の役割とプリオン蛋白質との相互作用 (2009)
  • Author(s): 松原岳大
  • Organizer: 日本薬理学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-03-16
• [Remarks] ホームページ等