運動系における情報伝達

• 研究課題/領域番号: 01623001
• 研究種目: 重点領域研究
• 配分区分: 補助金
• 研究機関: 名古屋大学
• 研究代表者: 永津 俊治 名古屋大学, 医学部, 教授 (40064802)
• 研究分担者: 川島 紘一郎 共立薬科大学, 薬学部, 教授 (50001037) ; 日高 弘義 名古屋大学, 医学部, 教授 (80100171) ; 永津 郁子 藤田学園保健衛生大学, 医学部, 教授 (80084573) ; 矢内原 昇 静岡県立大学, 薬学部, 教授 (80046250) ; 黒沢 良和 藤田学園保健衛生大学, 医学部, 教授 (10109259)
• 研究期間 (年度): 1989
• 研究課題ステータス: 完了 (1989年度)
• 配分額: 27,500千円 (直接経費: 27,500千円); 1989年度: 27,500千円 (直接経費: 27,500千円)
• キーワード: パーキンソン病 / 情報伝達 / ドパミン / チロシン水酸化酵素 / 遺伝子cDNA / フェニルエタノールアミン / アセチルコリン / カルモデュリン

研究概要

運動系における情報伝達は、ドパミンなどのアミン系伝達物質、ガンマアミノ酪酸のようなアミノ酸系伝達物質、多種の神経ペプチドによって制御されている。シナプス前部神経伝達物質とシナプス後部の情報受容変換機構の分子レベルより解明を続けた。パーキンソン病の分子生物学は、ドーパミンを中心とするカテコールアミンの合成酵素、特にチロシン水酸化酵素の遺伝子、MPTP様神経毒の探索と、その合成酵素と代謝酵素の遺伝子、の2方向より進んでいる。チロシン水酸化酵素、ドーパ脱炭酸酵素、ドーパミンβ-水酸化酵素、フェニールエタノールアミンN-メチル基転移酵素のすべてのヒトのカテコールアミン生合成酵素のcDNA、遺伝子DNAのクローニングに成功(永津、黒沢)、ヒトチロシン水酸化酵素関連ペプチドの化学合成(矢内原)、ヒト芳香族L-アミノ酸脱炭酸酵素cDNAのクローニングと塩基配列の決定(黒沢、永津)、パーキソン病に対するlevodopa過量投与の過酸化反応促進作用(小川)、中枢コリン作動性神経におけるアセチルコリン生合成機構の検討(川島)、細胞内のCa^<2+>の受容蛋白で細胞内の情報伝達系の最重要因子カルモデュリン結合81k蛋白質の発見(日高)、線条体と黒質におけるPKC各サイズタイプの局在と機能(田中)、運動制御系のシナプス伝達機序を明かにするために脳シナプス前膜のイオンチャンネルの存在の研究(渡辺)、胎生後期から生後にかけて一過性に出現するチロシン水酸化酵素・免疫陽性細胞を、マウスの前嗅核領域と、大脳皮質に発見(永津郁)、新生児期一側大脳皮質障害後の大脳皮質脊髄路の再構成(島田)、一側脳基底核に病変を持つ症例の終夜睡眠ポリグラフの研究(瀬川)、MPTP投与マウスにおけるパーキンソン病の発症機構と免疫系の研究(永津)以上の生理病理における運動系関連伝達物質の新しい知見は、パーキンソン病などの運動系疾患の情報伝達の異常の分子機構解明に重要な手がかりを与えた。

研究成果

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