Langston J W, Sastry S, Chan P, Forno L S, Bolin L M, Di Monte D A
The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089, USA.
Exp Neurol. 1998 Dec;154(2):684-90. doi: 10.1006/exnr.1998.6975.
A specific mutation (A53T) in the encoding region for alpha-synuclein has been identified in a large multigenerational family with an autosomal dominant parkinsonism known as the Contursi kindred. In this study, we used a monoclonal antibody directed against alpha-synuclein in order to identify novel proteins in the brain of an affected member of this kindred who had come to autopsy. Homogenates from the frontal cortex and caudate nucleus were examined using Western blot techniques and compared to matched autopsy specimens from control subjects and patients with various forms of parkinsonism. Western blots, using a 15-min exposure time, revealed the expected 19-kDa band representing alpha-synuclein in all brain samples examined. However, a novel band in the 36-kDa range was also present in the Contursi brain which was not seen in cortex or caudate from control brains or in frontal cortex from 14 cases of typical Parkinson's disease. With a 24-h exposure time, this band was faintly seen in the caudate nucleus of three of the Parkinson's disease cases. Surprisingly, the 36-kDa band (as well as other high-molecular-weight bands) was also present in frontal cortex and caudate nucleus in 3 additional cases that met diagnostic criteria for both Parkinson's disease and Alzheimer's disease. A preliminary analysis of samples from the frontal cortex of 10 Alzheimer's disease cases revealed a 36-kDa band in only one instance. The identification of novel alpha-synuclein-immunoreactive bands in these various forms of parkinsonism may open new research avenues for exploring the relationship between abnormal protein deposition in the brain and one or more neurodegenerative disorders, including the Contursi form of familial parkinsonism.
在一个患有常染色体显性帕金森症的大家族（称为孔图尔西家族）中，已在α-突触核蛋白编码区鉴定出一种特定突变（A53T）。在本研究中，我们使用一种针对α-突触核蛋白的单克隆抗体，以鉴定该家族一名已进行尸检的患病成员大脑中的新蛋白质。使用蛋白质印迹技术检测额叶皮质和尾状核的匀浆，并与来自对照受试者和患有各种形式帕金森症患者的匹配尸检标本进行比较。蛋白质印迹在15分钟曝光时间下显示，在所检测的所有脑样本中都出现了预期的代表α-突触核蛋白的19 kDa条带。然而，在孔图尔西家族患者的大脑中还出现了一条36 kDa范围内的新条带，在对照大脑的皮质或尾状核以及14例典型帕金森病患者的额叶皮质中均未见到。在24小时曝光时间下，在3例帕金森病患者的尾状核中隐约可见这条带。令人惊讶的是，在另外3例同时符合帕金森病和阿尔茨海默病诊断标准的病例中，额叶皮质和尾状核中也存在36 kDa条带（以及其他高分子量条带）。对10例阿尔茨海默病病例额叶皮质样本的初步分析仅在1例中发现了36 kDa条带。在这些各种形式的帕金森症中鉴定出新的α-突触核蛋白免疫反应条带，可能为探索大脑中异常蛋白质沉积与一种或多种神经退行性疾病（包括孔图尔西型家族性帕金森症）之间的关系开辟新的研究途径。
