Anatomical localization of Leucine-rich repeat kinase 2 in mouse brain
Anatomical localization of Leucine-rich repeat kinase 2 in mouse brain
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DOI：
10.1016/j.neuroscience.2006.01.017
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Farrer, M
中科院分区：
文献类型：
--
作者：
Melrose, H;Lincoln, S;Farrer, M
富含亮氨酸的重复蛋白激酶2(LRRK2)的突变最近在常染色体显性遗传的迟发性帕金森病中被发现。LRRK2在脑中的表达已有报道，但目前尚无确切的解剖学信息。我们进行了原位杂交和定量逆转录聚合酶链式反应，以定位LRRK2在小鼠脑内的表达。我们发现LRRK2在纹状体、皮质和嗅结节中高表达，而在黑质中很少或没有表达，在帕金森病中多巴胺能神经元优先变性。这些发现表明，LRRK2mRNA在多巴胺感受区表达，而不是在多巴胺合成神经元中表达。与LRRK2在帕金森病中的作用一致，多巴胺神经支配区域中富含亮氨酸的重复蛋白2蛋白的功能障碍可能导致多巴胺能神经传递的改变和黑质-纹状体通路的退化。(C)2006年由爱思唯尔有限公司代表IBRO出版。
Mutations in, leucine-rich repeat kinase 2 (LRRK2) have recently been identified in autosomal dominant late-onset Parkinson's disease. Expression of LRRK2 has previously been reported in brain; however, no precise anatomical information is yet available. We have performed in situ hybridization and quantitative reverse transcription polymerase chain reaction to map LRRK2 mRNA expression in mouse brain. We find LRRK2 is highly expressed in the striatum, cortex and olfactory tubercle; however, little or no expression is found in the substantia nigra, where dopaminergic neurons preferentially degenerate in Parkinson's disease. These findings suggest that LRRK2 mRNA is expressed in dopamine-receptive areas rather than in the dopamine-synthesizing neurons. Consistent with a role LRRK2 in Parkinson's disease, dysfunction of leucine-rich repeat kinase 2 protein in dopamine-innervated areas may to lead to altered dopaminergic neurotransmission and degeneration of the nigro-striatal pathway. (c) 2006 Published by Elsevier Ltd on behalf of IBRO.