Melrose H, Lincoln S, Tyndall G, Dickson D, Farrer M
Department of Neuroscience, Genetics of Parkinsonism and Related Disorders, Morris K. Udall Parkinson's Disease Research Center of Excellence, Birdsall Building, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Neuroscience. 2006;139(3):791-4. doi: 10.1016/j.neuroscience.2006.01.017. Epub 2006 Feb 28.
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.
富含亮氨酸重复激酶2（LRRK2）的突变最近在常染色体显性晚发性帕金森病中被发现。此前已有报道称LRRK2在大脑中表达；然而，尚无精确的解剖学信息。我们进行了原位杂交和定量逆转录聚合酶链反应，以绘制LRRK2 mRNA在小鼠大脑中的表达图谱。我们发现LRRK2在纹状体、皮质和嗅结节中高度表达；然而，在黑质中几乎没有发现表达，而在帕金森病中多巴胺能神经元优先在黑质退化。这些发现表明LRRK2 mRNA在多巴胺接受区域而非多巴胺合成神经元中表达。与LRRK2在帕金森病中的作用一致，富含亮氨酸重复激酶2蛋白在多巴胺支配区域的功能障碍可能导致多巴胺能神经传递改变和黑质纹状体通路退化。
