Molecular network of microRNA targets in Alzheimer's disease brains.

MicroRNAs (miRNAs) are a group of small noncoding RNAs that regulate translational repression of target mRNAs. The vast majority of presently identified miRNAs are expressed in the brain where they fine-tune the expression of a wide range of target molecules essential for neuronal and glial development, differentiation, proliferation, apoptosis and metabolism. Aberrant expression and dysfunction of brain-enriched miRNAs induce development of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Because a single miRNA concurrently downregulates hundreds of target mRNAs, the set of miRNA target genes coregulated by an individual miRNA generally constitutes the biologically integrated network of functionally associated molecules. Recent advances in systems biology enable us to characterize the global molecular network of experimentally validated targets for individual miRNAs by using pathway analysis tools of bioinformatics endowed with comprehensive knowledgebase. This review is conducted to summarize accumulating studies focused on aberrant miRNA expression in AD brains, and to propose the systems biological view that abnormal regulation of cell cycle progression as a result of deregulation of miRNA target networks plays a central role in the pathogenesis of AD.