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
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