Parkinsonism-inducing mechanism by endogenous multifunctional neurotoxins in the brain

脑内源性多功能神经毒素诱发帕金森病的机制

• 批准号: 16390041
• 负责人: OHTA Shigeru
• 金额: $ 8.38万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390041/
• 关键词: tetrahydroisoguinoline; Parkinson's disease; P-glycoprotein; drug transporter; expression level; テトラヒドロイソキノリン酸

We are investigating multiple functions of neurotoxic tetrahydroisoquinoline (TIQ) derivatives. In the present study, we examined the effects of TIQ derivatives on transporters such as P-glycoprotein (P-gp). Some of TIQ derivatives were recognized by P-gp and evacuated from the brain. The administration of TIQ derivatives to P-gp -inhibited mice promoted parkinsonism. Treatment of TIQ derivatives also change the expression level of P-gp : P-gp expression transiently went up, and then decreased. Thus, malfunction of P-gp is a candidate of Parkinson's disease-inducing factors.

我们正在研究神经毒性四氢异喹啉（TIQ）衍生物的多种功能。在本研究中，我们研究了TIQ衍生物对转运蛋白如P-糖蛋白（P-gp）的影响。部分TIQ衍生物可被P-gp识别并从脑内排出。对P-gp抑制小鼠给予TIQ衍生物可促进帕金森病。TIQ衍生物处理也改变了P-gp的表达水平：P-gp表达短暂升高，然后下降。因此，P-gp功能障碍是帕金森病诱发因素的候选者。

项目成果

Glutamate excitotoxicity is involved in cell death caused by tributyltin in cultured rat cortical neurons

• DOI: 10.1093/toxsci/kfj007
• 发表时间: 2006-01-01
• 期刊: TOXICOLOGICAL SCIENCES
• 影响因子: 3.8
• 作者: Nakatsu, Y;Kotake, Y;Ohta, S
• 通讯作者: Ohta, S

Tributyltin-induced cell death is mediated by calpain in PC12 cells

• DOI: 10.1016/j.neuro.2006.03.010
• 发表时间: 2006-07-01
• 期刊: NEUROTOXICOLOGY
• 影响因子: 3.4
• 作者: Nakatsu, Yusuke;Kotake, Yaichiro;Ohta, Shigeru
• 通讯作者: Ohta, Shigeru

Neuroprotective effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline on cultured rat mesencephalic neurons in the presence or absence of various neurotoxins

• DOI: 10.1016/j.brainres.2004.11.019
• 发表时间: 2005-02-08
• 期刊: BRAIN RESEARCH
• 影响因子: 2.9
• 作者: Kotake, Y;Taguchi, R;Ohta, S
• 通讯作者: Ohta, S

Parkinsonism-preventing activity of 1-methyl-1,2,3,4-tetrahydroisoquinoline derivatives in C57BL mouse in vivo.

• DOI: 10.1248/bpb.29.1401
• 发表时间: 2006-07
• 期刊: Biological & pharmaceutical bulletin
• 影响因子: 2
• 作者: K. Okuda;Y. Kotake;S. Ohta

Detection and determination of reticuline and N-methylcoculaurine in the Annonaceae family using liquid chromatography-tandem mass spectrometry.

液相色谱-串联质谱法检测和测定番荔枝科植物中的网脉碱和N-甲基红花碱。

• 发表时间: 2004
• 期刊: J.Chromatography B. 806
• 作者: Y.Kotake;et al.;Kotake Y. et al.
• 通讯作者: Kotake Y. et al.