2001 Fiscal Year Annual Research Report

アルツハイマー病における神経細胞死の機序―シグナル伝達の解析―

Research Project

Project/Area Number	11670617
Research Institution	Fukui Medical University
Principal Investigator	栗山勝福井医科大学, 医学部, 教授 (80107870)
Co-Investigator(Kenkyū-buntansha)	藤山二郎福井医科大学, 医学部・附属病院, 助手 (40283171) 武藤多津郎福井医科大学, 医学部・附属病院, 講師 (60190857)
Keywords	アミロイドβ蛋白 / アポトーシス / PC12 / 受容体チロシンキナーゼ / TrkA / リン酸化反応
Research Abstract	家族性アルツハイマー病の原因遺伝子であるプレセニリン-1(PS1)が神経成長因子受容体(Trk)に及ぼす影響を検討した。PS1を発現している野生型の神経芽細胞腫細胞(SH-SY5Y)、正常PS1を過剰制御発現した神経芽細胞腫細胞(SH20-3)、変異型PS1を発現した神経芽細胞腫細胞(SH-34.5)、mock(SH33-1)の各々の培養細胞を用いた。NGFで一定時間刺激後lysis bufferで可溶化、抗Trk抗体で免疫沈下し、抗一燐酸化チロシン抗体(α-PY)、抗Trkでイムノブロットを行った。 (1)各細胞に発現しているT-kの蛋白量には差違を認めなかったが、野生型PS1を過剰発現したSH20-3では、mock(SH33-1)に比べて明らかにNGFに対する反応性の低下を認めた。 (2)SH-34.5ではチロシン蛋白燐酸化反応の低下を認めた. (3)PS{の発現はSH-34.5では細胞質内に認められた. TrkとPS1との間にクロストークが存在し,互いに密接に調節いる事が推測された.

Research Products

(6 results)

All Other

All Publications (6 results)

[Publications] Hirayama M, et al.: "Improvement of apraxia of eyelid opening by wearing goggles"Lancet. 356. 1413 (2000)
[Publications] Mutho T, et al.: "Unglycosylated Trk protein does not colocalize nor associate with ganglioside GMI in stable clone overexpressing Trk of PC12 cells (PCtrk)"Glycoconjugate Journal. 17. 233-237 (2000)
[Publications] Mutho T, et al.: "Decreased phosphorylation levels of Trk B neurotrophin receptor in the spinal cords from patients with amyotrophic lateral sclerosis"Neurochemical Research. 25. 239-245 (2000)
[Publications] Hirayama M, et al.: "MK-801 is cytotoxic to microglia in vitro and its cytotoxivity is attenuated by glutamate, other excitotoxic agents and atropine Possible presence of glutamate receptor and muscarinic receptor on microglia"Brain Research. 897. 204-206 (2001)
[Publications] Hamano T, et al.: "Spinal Cavitous Hemorrhagic Infarction with Abdominal Aortic Aneurysm"European Journal of Neurology. 46. 160-162 (2001)
[Publications] Nakagawa H, et al.: "Tyrosine phosphorylation of the catalytic subunit pllo of phospratidylinositol-3 kinase induced by HMG-CoA reductase inhibitor inhibits its kinase activity in L6 myoblasts"Febs Letters. 508. 53-56 (2001)

2001 Fiscal Year Annual Research Report

アルツハイマー病における神経細胞死の機序―シグナル伝達の解析―

Principal Investigator

栗山 勝 福井医科大学, 医学部, 教授 (80107870)

Research Products

[Publications] Hirayama M, et al.: "Improvement of apraxia of eyelid opening by wearing goggles"Lancet. 356. 1413 (2000)

[Publications] Mutho T, et al.: "Unglycosylated Trk protein does not colocalize nor associate with ganglioside GMI in stable clone overexpressing Trk of PC12 cells (PCtrk)"Glycoconjugate Journal. 17. 233-237 (2000)

[Publications] Mutho T, et al.: "Decreased phosphorylation levels of Trk B neurotrophin receptor in the spinal cords from patients with amyotrophic lateral sclerosis"Neurochemical Research. 25. 239-245 (2000)

[Publications] Hirayama M, et al.: "MK-801 is cytotoxic to microglia in vitro and its cytotoxivity is attenuated by glutamate, other excitotoxic agents and atropine Possible presence of glutamate receptor and muscarinic receptor on microglia"Brain Research. 897. 204-206 (2001)

[Publications] Hamano T, et al.: "Spinal Cavitous Hemorrhagic Infarction with Abdominal Aortic Aneurysm"European Journal of Neurology. 46. 160-162 (2001)

[Publications] Nakagawa H, et al.: "Tyrosine phosphorylation of the catalytic subunit pllo of phospratidylinositol-3 kinase induced by HMG-CoA reductase inhibitor inhibits its kinase activity in L6 myoblasts"Febs Letters. 508. 53-56 (2001)

栗山勝福井医科大学, 医学部, 教授 (80107870)