Expression of nicotinamide N-methyltransferase (EC 2.1.1.1) in the parkinsonian brain
Expression of nicotinamide N-methyltransferase (EC 2.1.1.1) in the parkinsonian brain
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DOI：
10.1093/jnen/61.2.111
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发表时间：
2002-02-01
影响因子：
3.2
通讯作者：
Ramsden, DB
中科院分区：
文献类型：
--
作者：
Parsons, RB;Smith, ML;Ramsden, DB
烟酰胺N-甲基转移酶（NNMT）被认为是帕金森病（PD）的环境和遗传因素之间的联系。因此，我们探讨了高水平的NNMT表达可能易患PD的假设。高mRNA表达的区域显示在脊髓，髓质和颞叶，最低的表达在小脑，丘脑底核和尾状核。使用2 NNMT抗体，蛋白质被证明是在颞叶，尾状核，脊髓，小脑的颗粒神经元，多巴胺能神经元在黑质，和第三神经的轴突中的多极神经元的表达。比较帕金森病和非帕金森病对照组小脑和尾状核中NNMT的表达。PD组织表现出显著增加的NNMT蛋白和活性水平。PD病程与小脑表达水平呈负相关。这是第一次证明PD患者的脑组织中NNMT活性和蛋白质水平高于无PD患者，并且NNMT表达与PD中退化的神经元相关。
Nicotinamide N-methyltransferase (NNMT) has been proposed as a link between the environmental and genetic factors of Parkinson disease (PD). Therefore, we explored the hypothesis that high levels of NNMT expression may predispose to the development of PD. Regions of high mRNA expression were shown in the spinal cord, medulla, and temporal lobe, with lowest expression in the cerebellum, subthalamic nucleus, and caudate nucleus. Using 2 NNMT antibodies, the protein was shown to be expressed in multipolar neurons in the temporal lobe, caudate nucleus, and spinal cord, granular neurons of the cerebellum, dopaminergic neurons in the substantia nigra, and in the axons of the third nerve. Expression of NNMT was compared in PD and non-PD control cerebella and caudate nucleus. PD tissue exhibited significantly increased levels of NNMT protein and activity. PD disease duration was inversely correlated with the level of expression in cerebellum. This is the first demonstration that patients with PD have higher levels of NNMT activity and protein in brain tissue than those without PD and that NNMT expression is associated with neurons that degenerate in PD.