Jiao Fengjuan, Wang Qingzhi, Zhang Pei, Bu Lulu, Yan Jianguo, Tian Bo
Department of Neurobiology, Tongji Medical School, Huazhong University of Science and Technology, 13th Hangkong Road, Wuhan, Hubei Province, 430030, PR China; Key Laboratory of Neurological Diseases, Ministry of Education, 13 Hangkong Road, Wuhan, Hubei Province, 430030, PR China; Institute for Brain Research, Huazhong University of Science and Technology, 13th Hangkong Road, Wuhan, Hubei Province, 430030, PR China.
Department of Neurobiology, Tongji Medical School, Huazhong University of Science and Technology, 13th Hangkong Road, Wuhan, Hubei Province, 430030, PR China; Key Laboratory of Neurological Diseases, Ministry of Education, 13 Hangkong Road, Wuhan, Hubei Province, 430030, PR China; Institute for Brain Research, Huazhong University of Science and Technology, 13th Hangkong Road, Wuhan, Hubei Province, 430030, PR China.
Behav Brain Res. 2017 Jul 28;331:123-130. doi: 10.1016/j.bbr.2017.04.044. Epub 2017 May 2.
Parkinson's disease (PD) is an age-dependent neurodegenerative disease that can be caused by a variety of factors. Growing evidence shows that prior to the motor phase of PD can express molecular or imaging markers. Many long non-coding RNAs (lncRNAs) have been identified in neurodegenerative disease. However, the biogenesis and function of lncRNAs in the pre-symptomatic stage of PD is poorly understood. Here, we profiled the expression of lncRNAs and mRNAs in the substantia nigra pars compacta (SNpc) of pre-symptomatic mice over-expressing human A30PA53T α-synuclein by microarray analysis. Based on the Pearson correlation analysis, lncRNA/mRNA co-expression network was constructed. GO enrichment and pathway analysis of lncRNAs-coexpressed mRNAs was conducted to identify the related biological function and pathologic pathways. Real-time PCR was used to detect the expression pattern of lncRNAs. Approximately 756 lncRNAs were aberrantly expressed in the SNpc of early over-expressing human A30PA53T α-synuclein transgenic mice, including 477 downregulated lncRNAs and 279 upregulated lncRNAs. GO analysis indicated that these lncRNAs-coexpressed mRNAs were targeted to regulation of transcription (ontology: biological process), membrane (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis indicated that lncRNAs-coexpressed mRNAs were mostly enriched in axon guidance signaling pathway. In conclusion, the present study firstly identified a series of novel early PD-associated lncRNAs caused by mutant α-synuclein. Further study the function of these aberrantly expressed lncRNAs may provide insight into treatment of early PD.
帕金森病（PD）是一种与年龄相关的神经退行性疾病，可由多种因素引起。越来越多的证据表明，在帕金森病运动期之前可表现出分子或影像学标志物。在神经退行性疾病中已鉴定出许多长链非编码RNA（lncRNA）。然而，lncRNA在帕金森病症状前期的生物发生和功能尚不清楚。在此，我们通过微阵列分析对过表达人A30PA53Tα-突触核蛋白的症状前小鼠黑质致密部（SNpc）中的lncRNA和mRNA表达进行了分析。基于Pearson相关性分析，构建了lncRNA/mRNA共表达网络。对lncRNA共表达的mRNA进行GO富集和通路分析，以确定相关的生物学功能和病理通路。采用实时PCR检测lncRNA的表达模式。在早期过表达人A30PA53Tα-突触核蛋白转基因小鼠的SNpc中，约756个lncRNA异常表达，其中477个lncRNA下调，279个lncRNA上调。GO分析表明，这些lncRNA共表达的mRNA靶向转录调控（本体：生物学过程）、膜（本体：细胞成分）和蛋白质结合（本体：分子功能）。通路分析表明，lncRNA共表达的mRNA主要富集于轴突导向信号通路。总之，本研究首次鉴定出一系列由突变α-突触核蛋白引起的新型早期帕金森病相关lncRNA。进一步研究这些异常表达的lncRNA的功能可能为早期帕金森病的治疗提供思路。
