Girault J A, Raisman-Vozari R, Agid Y, Greengard P
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021.
Proc Natl Acad Sci U S A. 1989 Apr;86(7):2493-7. doi: 10.1073/pnas.86.7.2493.
This study was undertaken to evaluate the levels of cAMP-regulated phosphoproteins in the striatum of patients with neurodegenerative diseases of the dopaminergic system. Postmortem samples of caudate nucleus and putamen from 24 control subjects, 23 patients with Parkinson disease, and 13 patients with progressive supranuclear palsy were studied with immunoblotting techniques. The levels of tyrosine hydroxylase were reduced in patients with Parkinson disease (levels were 24% and 10% of controls in caudate nucleus and putamen, respectively) and with progressive supranuclear palsy (levels were 11% and 6% of controls in caudate nucleus and putamen, respectively). Five phosphoproteins, which are present in striatal neurons and are likely to play a role in the postsynaptic actions of dopamine, were measured. These included ARPP-16, ARPP-19, ARPP-21 (cAMP-regulated phosphoproteins of Mr 16,000, 19,000, and 21,000, respectively), DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32,000), and phosphatase inhibitor I. The levels of these phosphoproteins were inversely correlated with postmortem delay. In brains of patients with Parkinson disease or progressive supranuclear palsy with postmortem delays comparable to those of controls, the levels of these proteins as well as those of synaptic (synapsin I and synaptophysin) and glial (glial fibrillary acidic protein and myelin basic protein) markers were not significantly modified. We conclude that the levels of several phosphoproteins involved in signal transduction in striatal neurons are not altered in Parkinson disease and progressive supranuclear palsy. This observation supports the view that the striatal output neurons are intact in both diseases.
本研究旨在评估多巴胺能系统神经退行性疾病患者纹状体中cAMP调节的磷蛋白水平。采用免疫印迹技术对24名对照受试者、23名帕金森病患者和13名进行性核上性麻痹患者的尾状核和壳核尸检样本进行了研究。帕金森病患者和进行性核上性麻痹患者的酪氨酸羟化酶水平均降低（尾状核和壳核中的水平分别为对照的24%和10%以及11%和6%）。测量了存在于纹状体神经元中且可能在多巴胺突触后作用中发挥作用的五种磷蛋白。这些包括ARPP - 16、ARPP - 19、ARPP - 21（分别为分子量16,000、19,000和21,000的cAMP调节磷蛋白）、DARPP - 32（分子量32,000的多巴胺和cAMP调节磷蛋白）以及磷酸酶抑制剂I。这些磷蛋白的水平与尸检延迟呈负相关。在帕金森病或进行性核上性麻痹患者的大脑中，其尸检延迟与对照组相当，这些蛋白质以及突触（突触素I和突触囊泡蛋白）和胶质细胞（胶质纤维酸性蛋白和髓鞘碱性蛋白）标志物的水平没有显著改变。我们得出结论，纹状体神经元中参与信号转导的几种磷蛋白水平在帕金森病和进行性核上性麻痹中没有改变。这一观察结果支持了在这两种疾病中纹状体输出神经元完好无损的观点。
