A microRNA microarray analysis of C.elegans Parkinsons disease models

MicroRNAs (miRNAs) play an important role in human brain development and maintenance. To search for miRNAs potentially involved with molecular mechanisms in the pathogenesis of Parkinsons disease (PD), we utilized miRNA microarrays to identify expression changes of 115 annotated Caenorhabditis elegans (C.elegans) miRNAs in human -synuclein A53T transgenic, dopamine deficient catecholamine transporter gene cat-1 mutant and parkin gene pdr-1 mutant C.elegans strains. Twelve miRNAs were found regulated differentially in -synuclein transgenic C. elegans, five in cat-1 mutants and three in pdr-1 mutants. The family of miR64/65 appeared co-under-expressed in -synuclein and cat-1 strains and members of let-7 family co-under-expressed (except miR-241 over-expressed) in a-synuclein and pdr-1 strains. Class H serpentine receptor (srh) family of G-protein-coupled receptor genes were computationally identified to be highly over-represented target candidates for regulated miRNAs.These results indicate that miRNAs are misregulated in C. elegans PD models and suggest a role for these molecules in the disease pathogenesis.微小RNA（miRNAs）在人类大脑发育与维持过程中发挥着关键作用。为探寻可能参与帕金森病（PD）发病相关分子机制的miRNAs，本研究借助miRNA微阵列技术，对115种已注释的秀丽隐杆线虫（Caenorhabditis elegans，C.elegans）miRNAs在以下三种秀丽隐杆线虫菌株中的表达变化进行鉴定：过表达人源α-突触核蛋白A53T的转基因菌株、多巴胺缺陷型儿茶酚胺转运蛋白基因cat-1突变菌株，以及帕金基因pdr-1突变菌株。实验结果显示，在过表达α-突触核蛋白的秀丽隐杆线虫中共有12种miRNAs出现差异表达，cat-1突变菌株中检测到5种，pdr-1突变菌株中则有3种。miR64/65家族在过表达α-突触核蛋白与cat-1突变菌株中均呈现共同下调表达；let-7家族成员（除miR-241为上调表达外）在过表达α-突触核蛋白与pdr-1突变菌株中同样出现共同下调表达。经计算预测鉴定，G蛋白偶联受体家族中的H类蛇型受体（srh）基因家族是差异表达miRNAs的富集度极高的靶标候选基因。上述结果表明，miRNAs在秀丽隐杆线虫PD模型中存在表达失调现象，提示这类分子可能参与帕金森病的发病过程。