LRRK2 I2020T mutation is associated with tau pathology
LRRK2 I2020T mutation is associated with tau pathology
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DOI：
10.1016/j.parkreldis.2012.03.024
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发表时间：
2012-08-01
影响因子：
4.1
通讯作者：
Hattori, Nobutaka
中科院分区：
文献类型：
--
作者：
Ujiie, Sachiko;Hatano, Taku;Hattori, Nobutaka
富含亮氨酸重复激酶 2 (LRRK2) 基因的突变是常染色体显性家族性帕金森病 (FPD) 的最常见原因。 LRRK2 相关 FPD 的可变病理特征3包括路易体、与轴突球体相关的前角细胞变性、神经原纤维缠结 (NFT) 和 43 kDa (TDP-43) 阳性包涵体的 TAR DNA 结合蛋白。此外，据报道，微管相关蛋白 tau 的异常过度磷酸化（部分由蛋白激酶催化产生）与包括 FPD 在内的许多疾病的进行性神经变性有关。因此，我们检查了 6 名携带 LRRK2 I2020T 突变（一种与 PARKS 相关的致病突变）的患者，发现脑干中存在异常 tau 磷酸化沉积。此外，我们发现 LRRK2 I2020T 在共表达 LRRK2-I2020T 和 3 或 4 重复 tau 的培养细胞中增强了 tau 磷酸化。这是第一份描述 tau 过度磷酸化与 LRRK2 I2020T 之间关系的报告。 (C) 2012 Elsevier Ltd. 保留所有权利。
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of autosornal-dominant familial Parkinson's disease (FPD). The variable pathological feature:3 of LRRK2-linked FPD include Lewy bodies, degeneration of anterior horn cells associated with axonal spheroids, neurofibrillary tangles (NFTs) and TAR DNA-binding protein of 43 kDa (TDP-43) positive inclusion bodies. Furthermore, abnormal hyperphosphorylation of microtubule associated protein tau, in part generated by catalysis of protein kinases, has been reported to be involved in progressive neurodegeneration in a number of diseases, including FPD. Thus, we examined six patients carrying the LRRK2 I2020T mutation, a pathogenic mutation associated with PARKS, and found abnormal tau phosphorylation depositions in the brainstem. Additionally, we found LRRK2 I2020T enhanced tau phosphorylation in cultured cells co-expressing LRRK2-I2020T and 3 or 4-repeated tau. This is the first report describing the relationship between hyperphosphorylation of tau and LRRK2 I2020T. (C) 2012 Elsevier Ltd. All rights reserved.