Abstract
MicroRNAs (miRNAs) are regulatory genetic elements that coordinate the expression of thousands of genes and play important roles in brain aging and neurodegeneration. DNA polymorphisms affecting miRNA biogenesis, dosage, and gene targeting may represent potentially functional variants. The consequences of single nucleotide polymorphisms affecting miRNA function were previously demonstrated by both experimental and computational methods. However, little is known about how copy number variations (CNVs) influence miRNA metabolism and regulatory networks. We discuss potential mechanisms of CNVs-mediated effects on miRNA function and regulation that might have consequences for brain aging. We argue that CNVs, which potentially can alter miRNA expression, regulation or target gene recognition, are possible functional variants and should be considered high priority candidates in genotype–phenotype mapping studies of brain-related disorders.
Highlights
The establishment of human cognitive abilities is a gradual process that takes place mostly in the period between birth and adulthood, some developmental processes extend beyond this period (Sowell et al, 2004; Thompson et al, 2004; Zhan et al, 2013)
The mechanisms that operate during the progress of brain aging and associated neurodegenerative diseases are complex and their malfunction is rarely due to the failure of a few cell death or neuronal differentiation genes
Because susceptibility to premature aging and cognitive decline is a result of the malfunction of numerous genes, miRNAs dysregulation that inevitably would alter the expression of multiple genes might provide the basis for neuronal cell deterioration
Summary
The establishment of human cognitive abilities is a gradual process that takes place mostly in the period between birth and adulthood, some developmental processes extend beyond this period (Sowell et al, 2004; Thompson et al, 2004; Zhan et al, 2013). The genome-wide expression analysis of miRNAs in aging individuals revealed a general decline in miRNA levels that was linked to potential loss of control of genes that regulate the cell cycle progression and cell differentiation programing (Noren Hooten et al, 2010). MicroRNAs play a role in the control of brain metabolism and subsequently the dynamic of miRNA expression levels reflects the cellular responses to aging progression and deterioration of neuronal functionality.
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