Weinberg Marc S, Wood Matthew J A
Department of Molecular Medicine and Haematology, University of the Witwatersrand Medical School, Parktown, South Africa.
Hum Mol Genet. 2009 Apr 15;18(R1):R27-39. doi: 10.1093/hmg/ddp070.
Genomic studies in model organisms and in humans have shown that complexity in biological systems arises not from the absolute number of genes, but from the differential use of combinations of genetic programmes and the myriad ways in which these are regulated spatially and temporally during development, senescence and in disease. Nowhere is this lesson in biological complexity likely to be more apparent than in the human nervous system. Increasingly, the role of genomic non-protein coding small regulatory RNAs, in particular the microRNAs (miRNAs), in regulating cellular pathways controlling fundamental functions in the nervous system and in neurodegenerative disease is being appreciated. Not only might dysregulated expression of miRNAs serve as potential disease biomarkers but increasingly such short regulatory RNAs are being implicated directly in the pathogenesis of complex, sporadic neurodegenerative disease. Moreover, the targeting and exploitation of short RNA silencing pathways, commonly known as RNA interference, and the development of related tools, offers novel therapeutic approaches to target upstream disease components with the promise of providing future disease modifying therapies for neurodegenerative disorders.
对模式生物和人类的基因组研究表明，生物系统的复杂性并非源于基因的绝对数量，而是源于遗传程序组合的差异使用，以及这些程序在发育、衰老和疾病过程中在空间和时间上被调控的无数方式。在生物复杂性方面，这一教训在人类神经系统中可能最为明显。越来越多的研究认识到，基因组非蛋白质编码小调节RNA，特别是微小RNA（miRNA），在调节控制神经系统基本功能和神经退行性疾病的细胞途径中所起的作用。miRNA表达失调不仅可能作为潜在的疾病生物标志物，而且这类短调节RNA越来越多地直接参与复杂的散发性神经退行性疾病的发病机制。此外，对通常称为RNA干扰的短RNA沉默途径的靶向和利用，以及相关工具的开发，为靶向疾病上游成分提供了新的治疗方法，有望为神经退行性疾病提供未来的疾病修饰疗法。
