Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies.
Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies.
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发表时间：
1998-04
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通讯作者：
M. Baba;S. Nakajo;Ping-Hui Tu;T. Tomita;K. Nakaya;V. Lee;J. Trojanowski;T. Iwatsubo
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作者：
M. Baba;S. Nakajo;Ping-Hui Tu;T. Tomita;K. Nakaya;V. Lee;J. Trojanowski;T. Iwatsubo
路易体（Lewy bodies，LB）是帕金森病（Parkinson's disease，PD）和路易体痴呆（Dementia with Lewy bodies，DLB）患者脑内退化神经元的标志性病变。最近，在一些常染色体显性遗传的家族性PD家系中发现了编码突触前α-突触核蛋白的基因的点突变，光镜研究表明α-突触核蛋白在散发性PD和DLB的LB中具有免疫反应性。为了表征LB中的α-突触核蛋白，我们提出了从DLB脑中纯化的LB的单克隆抗体（MAb），并获得了对α-突触核蛋白特异的MAb，其强烈标记LB。光和电子显微镜免疫细胞化学研究进行了这种单克隆抗体以及其他抗体的α和β-突触核蛋白表明，α-突触核蛋白，但不是β-突触核蛋白，是一个组成部分的LB在散发性PD和DLB。来自DLB脑的高度纯化的LB的蛋白质印迹分析表明，α-突触核蛋白的全长以及部分截短的和不溶性的聚集体沉积在LB中。因此，这些数据强烈暗示α-突触核蛋白在LB的形成和选择性变性的神经元在散发性PD和DLB。
Lewy bodies (LBs) are hallmark lesions of degenerating neurons in the brains of patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recently, a point mutation in the gene encoding the presynaptic alpha-synuclein protein was identified in some autosomal-dominantly inherited familial PD pedigrees, and light microscopic studies demonstrated alpha-synuclein immunoreactivity in LBs of sporadic PD and DLB. To characterize alpha-synuclein in LBs, we raised monoclonal antibodies (MAbs) to LBs purified from DLB brains and obtained a MAb specific for alpha-synuclein that intensely labeled LBs. Light and electron microscopic immunocytochemical studies performed with this MAb as well as other antibodies to alpha-and beta-synuclein showed that alpha-synuclein, but not beta-synuclein, is a component of LBs in sporadic PD and DLB. Western blot analyses of highly purified LBs from DLB brains showed that full-length as well as partially truncated and insoluble aggregates of alpha-synuclein are deposited in LBs. Thus, these data strongly implicate alpha-synuclein in the formation of LBs and the selective degeneration of neurons in sporadic PD and DLB.