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一种多巴胺能神经毒素,1(R),2(N)-二甲基-6,7-二羟基-1,2,3,4-四氢异喹啉、N-甲基(R)萨索林醇及其氧化产物1,2(N)-二甲基-6,7-二羟基异喹啉鎓离子,在人脑黑质纹状体系统中蓄积。

A dopaminergic neurotoxin, 1(R), 2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, N-methyl(R)salsolinol, and its oxidation product, 1,2(N)-dimethyl-6,7-dihydroxyisoquinolinium ion, accumulate in the nigro-striatal system of the human brain.

作者信息

Maruyama W, Sobue G, Matsubara K, Hashizume Y, Dostert P, Naoi M

机构信息

Department of Basic Gerontology, National Institute for Longevity Sciences, Obu, Japan.

出版信息

Neurosci Lett. 1997 Feb 14;223(1):61-4. doi: 10.1016/s0304-3940(97)13389-4.

Abstract

N-Methyl(R)salsolinol was found to be an endogenous dopaminergic neurotoxin inducing parkinsonism in rodents and to increase in the cerebrospinal fluid of parkinsonian patients. The amounts of N-methyl(R)salsolinol and related compounds in the human brain regions were quantitatively analyzed. Only the (R)-enantiomer of salsolinol derivatives were detected, which suggests their enzymatic synthesis in situ. In the nigro-striatal system, the concentration of N-methyl(+)salsolinol was higher than in the frontal cortex, and its oxidized catechol isoquinolinium ion was detected only in the substantia nigra significantly. The accumulation of these neurotoxins in the nigro-striatal region might account for selective cell death of dopamine neurons in the substantia nigra of Parkinson's disease.

摘要

N-甲基(R)-去甲猪毛菜酚被发现是一种内源性多巴胺能神经毒素,可在啮齿动物中诱发帕金森病,并在帕金森病患者的脑脊液中含量增加。对人脑中N-甲基(R)-去甲猪毛菜酚及相关化合物的含量进行了定量分析。仅检测到去甲猪毛菜酚衍生物的(R)-对映体,这表明它们是原位酶促合成的。在黑质纹状体系统中,N-甲基(+)-去甲猪毛菜酚的浓度高于额叶皮质,且其氧化的儿茶酚异喹啉离子仅在黑质中被显著检测到。这些神经毒素在黑质纹状体区域的积累可能是帕金森病患者黑质中多巴胺能神经元选择性死亡的原因。

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