Iwatsubo T
Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
Rinsho Shinkeigaku. 1999 Dec;39(12):1285-6.
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). DLB is the second most common neurodegenerative dementia after Alzheimer's disease, which is characterized clinically by fluctuating cognitive impairments, visual hallucinations and parkinsonism, and pathologically by the appearance of cortical LBs. To characterize the components of LBs, we have developed a purification procedure for LBs from cortices of patients with DLB using sucrose density separation followed by fluorescence-activated particle sorting. We then raised monoclonal antibodies (mAbs) to purified LBs, and obtained a mAb (LB509) that intensely immunolabeled LBs and specifically reacted with a approximately 18kDa brain protein, which was identified as alpha-synuclein. LB509 as well as other antibodies to alpha-synuclein, but not to beta-synuclein, immunostained brainstem and cortical LBs in sporadic PD and DLB brains. Recently, a point mutation in alpha-synuclein gene was identified in some autosomal-deminantly inherited familial PD pedigrees. Moreover, glial cytoplasmic inclusions in the brains of patients with multiple system atrophy (MSA) were shown to be alpha-synuclein positive. Taken together, our data strongly implicate alpha-synuclein in the formation of LBs and the selective neuronal degeneration in PD, DLB and MSA.
路易小体（LBs）是帕金森病（PD）和路易体痴呆（DLB）患者大脑中神经元退化的标志性病变。DLB是仅次于阿尔茨海默病的第二常见神经退行性痴呆，其临床特征为认知功能波动、视幻觉和帕金森综合征，病理特征为皮质路易小体的出现。为了表征路易小体的成分，我们开发了一种从DLB患者皮质中纯化路易小体的方法，采用蔗糖密度分离法，随后进行荧光激活颗粒分选。然后，我们针对纯化的路易小体产生了单克隆抗体（mAb），并获得了一种单克隆抗体（LB509），该抗体强烈免疫标记路易小体，并与一种约18kDa的脑蛋白特异性反应，该蛋白被鉴定为α-突触核蛋白。LB509以及其他针对α-突触核蛋白而非β-突触核蛋白的抗体，对散发性PD和DLB大脑中的脑干和皮质路易小体进行了免疫染色。最近，在一些常染色体显性遗传的家族性PD家系中发现了α-突触核蛋白基因的点突变。此外，多系统萎缩（MSA）患者大脑中的胶质细胞胞质内含物显示α-突触核蛋白呈阳性。综上所述，我们的数据强烈表明α-突触核蛋白与路易小体的形成以及PD、DLB和MSA中的选择性神经元退化有关。
