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路易小体中α-突触核蛋白、泛素和脂质共定位与分离的原位和体外研究

In situ and in vitro study of colocalization and segregation of alpha-synuclein, ubiquitin, and lipids in Lewy bodies.

作者信息

Gai W P, Yuan H X, Li X Q, Power J T, Blumbergs P C, Jensen P H

机构信息

Department of Physiology and Centre for Neuroscience, Flinders University, Bedford Park, South Australia, 5042, Australia.

出版信息

Exp Neurol. 2000 Dec;166(2):324-33. doi: 10.1006/exnr.2000.7527.

DOI:10.1006/exnr.2000.7527
PMID:11085897
Abstract

alpha-Synuclein and ubiquitin are two Lewy body protein components that may play antagonistic roles in the pathogenesis of Lewy bodies. We examined the relationship between alpha-synuclein, ubiquitin, and lipids in Lewy bodies of fixed brain sections or isolated from cortical tissues of dementia with Lewy bodies. Lewy bodies exhibited a range of labeling patterns for alpha-synuclein and ubiquitin, from a homogeneous pattern in which alpha-synuclein and ubiquitin were evenly distributed and overlapped across the inclusion body to a concentric pattern in which alpha-synuclein and ubiquitin were partially segregated, with alpha-synuclein labeling concentrated in the peripheral domain and ubiquitin in the central domain of the Lewy body. Lipids represented a significant component in both homogeneous and concentric Lewy bodies. These results suggest that Lewy bodies are heterogeneous in their subregional composition. The segregation of alpha-synuclein to Lewy body peripheral domain is consistent with the hypothesis that alpha-synuclein is continually deposited onto Lewy bodies.

摘要

α-突触核蛋白和泛素是路易小体的两种蛋白质成分,它们可能在路易小体的发病机制中发挥拮抗作用。我们研究了固定脑切片的路易小体中或从路易体痴呆患者皮质组织中分离出的路易小体中α-突触核蛋白、泛素和脂质之间的关系。路易小体呈现出一系列α-突触核蛋白和泛素的标记模式,从α-突触核蛋白和泛素均匀分布并在包涵体内重叠的均匀模式,到α-突触核蛋白和泛素部分分离的同心模式,其中α-突触核蛋白标记集中在路易小体的外周区域,泛素集中在路易小体的中心区域。脂质在均匀和同心路易小体中均占显著成分。这些结果表明路易小体在其亚区域组成上是异质性的。α-突触核蛋白向路易小体外周区域的分离与α-突触核蛋白不断沉积到路易小体上的假说一致。

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