Increased M-calpain expression in the mesencephalon of patients with Parkinson's disease but not in other neurodegenerative disorders involving the mesencephalon: A role in nerve cell death?
Increased M-calpain expression in the mesencephalon of patients with Parkinson's disease but not in other neurodegenerative disorders involving the mesencephalon: A role in nerve cell death?
复制标题
DOI：
10.1016/0306-4522(96)00100-5
复制
发表时间：
1996-08-01
期刊：
影响因子：
3.3
通讯作者：
Hirsch, EC
中科院分区：
文献类型：
--
作者：
MouattPrigent, A;Karlsson, JO;Hirsch, EC
帕金森氏病的特征在于黑质中多巴胺能神经元的缺失，并且在较小程度上，腹侧被盖区和儿茶酚胺能细胞群A8中多巴胺能神经元的缺失。然而，在这些多巴胺能神经元中，那些表达钙缓冲蛋白钙结合蛋白的神经元被选择性地保留，这表明细胞内钙浓度的升高可能参与了导致帕金森病神经细胞死亡的级联事件。因此，我们化学分析的表达的钙依赖性蛋白酶calpain II（m-钙蛋白酶）在中脑的帕金森氏病，进行性核上性麻痹或纹状体黑质变性，黑质多巴胺能神经元退化的患者，和匹配的控制没有黑质参与。Calpain免疫反应阳性细胞分布于黑质、腹侧被盖区、A8型儿茶酚胺能细胞群和蓝斑的纤维和神经元胞体。在帕金森氏病患者，但不是与其他神经退行性疾病，m-钙蛋白酶免疫反应性检测到异常形态的纤维和路易体。连续双染显示，大多数这些m-钙蛋白酶阳性纤维和神经元胞体共表达酪氨酸羟化酶，表明大多数m-钙蛋白酶神经元的儿茶酚胺。在黑质和蓝斑的m-钙蛋白酶染色的定量分析显示，帕金森病患者在这两个结构的纤维和神经元胞体密度增加，这些数据表明，钙浓度增加可能与帕金森病的神经细胞死亡。版权所有（C）1996 IBRO。
Parkinson's disease is characterized by the lass of dopaminergic neurons in the substantia nigra and, to a lesser extent, the ventral tegmental area and catecholaminergic cell group A8. However, among these dopaminergic neurons, those expressing the calcium buffering protein calbindin are selectively preserved, suggesting that a rise in intracellular calcium concentrations may be involved in the cascade of events leading to nerve cell death in Parkinson's disease. We therefore analysed immunohistochemically the expression of the calcium-dependent protease calpain II (m-calpain) in the mesencephalon of patients with Parkinson's disease, progressive supranuclear palsy or striatonigral degeneration, where nigral dopaminergic neurons degenerate, and matched controls without nigral involvement. Calpain immunoreactivity was found in fibers and neuronal perikarya in the substantia nigra, the ventral tegmental area, catecholaminergic cell group A8 and the locus coeruleus. In patients with Parkinson's disease but not with the other neurodegenerative disorders, m-calpain immunoreactivity was detected in fibers with an abnormal morphology and in Lewy bodies. Sequential double staining revealed that most of these m-calpain-positive fibers and neuronal perikarya co-expressed tyrosine hydroxylase, indicating that most m-calpain neurons are catecholaminergic. Quantitative analysis of m-calpain staining in the substantia nigra and locus coeruleus revealed an increased density of fibers and neuronal perikarya in parkinsonian patients in both structures.These data suggest that increased calcium concentrations may be associated with nerve cell death in Parkinson's disease. Copyright (C) 1996 IBRO.