Regulating mechanism for intracellular stability of tyrosine hydroxylase and neurodegeneration

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590946
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Fujita Health University
• Principal Investigator: NAKASHIMA Akira 藤田保健衛生大学, 医学部, 准教授 (20180276)
• Co-Investigator(Kenkyū-buntansha): OTA Akira 藤田保健衛生大学, 医学部, 教授 (10247637)
• Co-Investigator(Renkei-kenkyūsha): HAYASHI Nobuhiro 東京工業大学, 生命理工学研究科 (80267955)
• Project Period (FY): 2010 – 2012
• Keywords: 神経分子病態学 / パーキンソン病 / チロシン水酸化酵素

Research Abstract

We revealed that the phosphorylation of the N-terminal portion of tyrosine hydroxylase (TH) positively regulates the intracellular stability of the enzyme. The phosphorylation of two serine residues was shown to be a trigger for the proteasomedigestion. Moreover, 14-3-3 protein which is major protein in mammalian brain is a critical factor in regulating TH stability by acting to promote the degradation of TH phosphorylated at its N-terminus.

Research Products

• [Journal Article] Proteasomal degradation of tyrosine hydroxylase and neurodegeneration. (2012)
  • Author(s): Nakashima A.
  • Journal Title: J Neurochem. Volume: 120 Pages: 199-201
  • Peer Reviewed
• [Journal Article] A possible pathophysiological role of tyrosine hydroxylase in Parkinson's disease suggested by postmortem brainbiochemistry: a contribution for the special 70th birthday symposium in honor of Prof. Peter Riederer. (2012)
  • Author(s): Nakashima A, Ota A, Kaneko YS, Mori K, Nagasaki H and Nagatsu T.
  • Journal Title: J Neural Transm. Volume: 120 Pages: 49-45
  • Peer Reviewed
• [Journal Article] Phosphorylation of the N-terminal portion of tyrosine hydroxylase triggers proteasomal digestion of the enzyme. (2011)
  • Author(s): Nakashima A, Mori K, Kaneko YS, Hayashi N, Nagatsu T and Ota A.
  • Journal Title: Biochem Biophys Res Commun. Volume: 407 Pages: 343-347
  • Peer Reviewed
• [Journal Article] Intracellular stability of tyrosine hydroxylase: Phosphorylation and proteasomal digestion of the enzyme.
  • Author(s): Nakashima A, Kaneko YS, Kodani Y, Mori K, Nagasaki H, Nagatsu T and Ota A.
  • Journal Title: Adv Pharmacol.
  • Peer Reviewed
• [Presentation] Phosphorylation and proteasomal digestion of tyrosine hydroxylase. (2012)
  • Author(s): Nakashima A, Kaneko YS, Mori K, Nagasaki H, Nagatsu T and Ota A.
  • Organizer: The 11th Biennial Meeting of APSN and 55th Meeting of JSN
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2012-10-01
• [Presentation] Intracellular stability of tyrosine hydroxylase: phosphorylation and proteasomal digestion of the enzyme. (2012)
  • Author(s): Nakashima A, Kaneko YS, Mori K, Nagasaki H, Nagatsu T and Ota A.
  • Organizer: The Tenth International Catecholamine Symposium
  • Place of Presentation: Asilomar, CA. USA.
  • Year and Date: 2012-09-11
• [Presentation] Intracellular degradation and localization of tyrosine hydroxylase. (2012)
  • Author(s): Nakashima A, Mori K, Kaneko YS, Nagasaki N, Nagatsu T and Ota A.
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 松本市
  • Year and Date: 2012-03-30
• [Presentation] Intracellular degradation and localization of tyrosine hydroxylase; phosphorylation and proteasomal digestion of the enzyme. (2011)
  • Author(s): Nakashima A, Mori K, Kaneko YS, Nagasaki H, Hayashi H, Nagatsu T and Ota A.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Washington D.C., USA
  • Year and Date: 2011-11-13