A comparative analysis of leucine-rich repeat kinase 2 (Lrrk2) expression in mouse brain and Lewy body disease
A comparative analysis of leucine-rich repeat kinase 2 (Lrrk2) expression in mouse brain and Lewy body disease
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DOI：
10.1016/j.neuroscience.2007.05.027
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发表时间：
2007-07-29
期刊：
影响因子：
3.3
通讯作者：
Farrer, M. J.
中科院分区：
文献类型：
--
作者：
Melrose, H. L.;Kent, C. B.;Farrer, M. J.
富亮氨酸重复激酶2 （LRRK2, LRRK2）的致病性替代与家族性晚发性帕金森病有遗传联系。终末期疾病主要与神经神经元丢失和路易体病理相关，但患者可能有胶质细胞增生、tau或泛素包涵体（多形性病理）。Lrrk2蛋白的解剖分布可能有助于了解其在健康和神经退行性疾病中的功能，因此，我们使用野生型和人类Lrrk2转基因细菌人工染色体（BAC）小鼠以及弥漫性路易体病（DLBD）患者的脑组织，对“内部”和市售的Lrrk2抗体进行了比较研究。Lrrk2蛋白在包括黑质、丘脑和纹状体在内的大多数脑区普遍表达且相对丰富。Lrrk2不是路易体或与帕金森病相关的神经炎病理的主要成分。然而，lrrk2相关帕金森氏症中多巴胺能神经元的选择性丧失认为该蛋白可能具有区域特异性相互作用。Lrrk2免疫组织化学染色存在于心室下区，这是一个包含干细胞的区域，可以产生神经元和胶质细胞。Lrrk2在神经发生中的作用可能为进一步了解突变蛋白在年龄相关神经变性多形性病理中的异常作用提供帮助。(c) 2007 ibro。Elsevier Ltd.出版。版权所有。
Pathogenic substitutions in leucine-rich repeat kinase 2 (LRRK2, Lrrk2) have been genetically linked to familial, late-onset Parkinsonism. End-stage disease is predominantly associated with nigral neuronal loss and Lewy body pathology, but patients may have gliosis, tau or ubiquitin inclusions (pleomorphic pathology). The anatomical distribution of Lrrk2 protein may provide insight into its function in health and neurodegeneration, thus we performed a comparative study with 'in-house' and commercially available Lrrk2 antibodies using brain tissue from wild type and human Lrrk2 transgenic bacterial artificial chromosome (BAC) mice, and from diffuse Lewy body disease (DLBD) patients. Lrrk2 protein was ubiquitously expressed and relatively abundant in most brain regions, including the substantia nigra, thalamus and striatum. Lrrk2 was not a major component of Lewy body or neuritic pathology associated with Parkinson's disease. However, selective loss of dopaminergic neurons in Lrrk2-associated Parkinsonism argues the protein may have regional-specific interactions. Lrrk2 immunohistochemical staining was present in the subventricular zone, a region containing stem cells that give rise to both neurons and glia. A role for Lrrk2 in neurogenesis might provide further insight into the aberrant role of mutant protein in age-associated neurodegeneration with pleomorphic pathology. (C) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.