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帕金森病脑中 1-乙酰基-6,7-二羟基-1,2,3,4-四氢异喹啉(ADTIQ)类似物的出现和分布。

Occurrence and distribution of salsolinol-like compound, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (ADTIQ) in parkinsonian brains.

机构信息

School of Life Science, Beijing Institute of Technology, Beijing, 100081, China.

出版信息

J Neural Transm (Vienna). 2012 Apr;119(4):435-41. doi: 10.1007/s00702-011-0724-4. Epub 2011 Nov 8.

Abstract

Parkinson's disease (PD) arises from the loss of dopaminergic neurons in the substantia nigra. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is well known to cause Parkinsonism in humans with neurotoxicity specific for dopaminergic neurons. The experience with MPTP supports the hypothesis that endogenous or xenobiotic neurotoxins are involved in the pathogenesis of PD in humans. In our study, 1-acetyl-6, 7-dihydroxy-1, 2, 3, 4-tetrahydro-isoquinoline (ADTIQ), a novel compound, was found in frozen human brain tissues. The formation of ADTIQ was demonstrated using dopamine and methylglyoxal under physiological conditions. Methylglyoxal is a by-product of glycolysis. ADTIQ and its precursors, dopamine and methylglyoxal, were detected in different regions of frozen human brains such as the substantia nigra, caudate nucleus, putamen, frontal cortex, and the cerebellum. A significant difference in ADTIQ levels between control and Parkinson's patients was found; for instance, the ADTIQ level in putamen of PD patients was 0.76 ± 0.27 nmol/g compared to 0.10 ± 0.01 nmol/g in control. Our results might indicate that ADTIQ is possibly related to Parkinson's disease.

摘要

帕金森病(PD)源于黑质中多巴胺能神经元的丧失。1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)众所周知可引起人类帕金森病,对多巴胺能神经元具有神经毒性。MPTP 的经验支持这样一种假设,即内源性或外源性神经毒素参与了人类 PD 的发病机制。在我们的研究中,在冷冻的人脑组织中发现了 1-乙酰基-6,7-二羟基-1,2,3,4-四氢异喹啉(ADTIQ),这是一种新型化合物。在生理条件下使用多巴胺和甲基乙二醛证明了 ADTIQ 的形成。ADTIQ 及其前体多巴胺和甲基乙二醛存在于不同的冷冻人脑区域,如黑质、尾状核、壳核、额叶皮质和小脑。在帕金森病患者和对照组之间发现了 ADTIQ 水平的显著差异;例如,PD 患者壳核中的 ADTIQ 水平为 0.76±0.27 nmol/g,而对照组为 0.10±0.01 nmol/g。我们的结果可能表明 ADTIQ 可能与帕金森病有关。

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