Leucine-rich repeat kinase 2 colocalizes with alpha-synuclein in Parkinson's disease, but not tau-containing deposits in tauopathies.
Leucine-rich repeat kinase 2 colocalizes with alpha-synuclein in Parkinson's disease, but not tau-containing deposits in tauopathies.
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在帕金森病中，富含亮氨酸的重复激酶 2 与 α-突触核蛋白共定位，但在 tau 病中则不与含有 tau 的沉积物共定位。
DOI：
10.1159/000113708
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Chen,ShuG
中科院分区：
文献类型：
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作者：
Perry,George;Zhu,Xiongwei;Babar,AsimK;Siedlak,SandraL;Yang,Qiwei;Ito,Genta;Iwatsubo,Takeshi;Smith,MarkA;Chen,ShuG
背景：富亮氨酸重复激酶2 （LRRK2）突变是迄今为止常染色体显性和特发性帕金森病最常见的遗传原因。目的：利用LRRK2的高特异性抗体，探讨LRRK2是否与帕金森病、路易体痴呆等相关疾病的病理结构直接相关。结果：LRRK2抗体强烈标记脑干和皮层路易体，分别是帕金森病和痴呆伴路易体的病理标志。我们发现20-100%（平均60%）α-synuclein阳性的路易小体含有LRRK2。虽然先前在Western blots上显示针对LRRK2不同区域的抗体可以标记重组LRRK2，但只有针对N和c端而不是包含LRRK2折叠蛋白结构域的区域的抗体可以免疫标记路易小体。在阿尔茨海默病中，发现平野体含有LRRK2，而进行性核上性麻痹的神经原纤维缠结仍未标记。结论：在正常和病理条件下，LRRK2的细胞定位信息将加深我们对其功能和与帕金森病及相关疾病进展相关的分子途径的理解。
Background:Mutations in leucine-rich repeat kinase 2 (LRRK2) are thus far the most frequent genetic cause associated with autosomal dominant and idiopathic Parkinson’s disease.Objective:To examine whether LRRK2 is directly associated with the pathological structures of Parkinson’s disease, dementia with Lewy bodies, and other related disorders using highly specific antibodies to LRRK2.Results:LRRK2 antibodies strongly labeled brainstem and cortical Lewy bodies, the pathological hallmarks of Parkinson’s disease and dementia with Lewy bodies, respectively. We found that 20–100% (mean 60%) of α-synuclein-positive Lewy bodies contained LRRK2. While antibodies raised against various regions of LRRK2 were previously shown to label recombinant LRRK2 on Western blots, only antibodies raised against the N- and C-termini, but not the regions containing folded protein domains of LRRK2, immunolabeled Lewy bodies. In Alzheimer’s disease, Hirano bodies were found to contain LRRK2 and the neurofibrillary tangles in progressive supranuclear palsy remained unlabeled.Conclusions:Information on the cellular localization of LRRK2 under normal and pathological conditions will deepen our understanding of its functions and molecular pathways relevant to the progression of Parkinson’s disease and related disorders.