Abstract
Generated by the ribonuclease III Dicer, microRNAs (miRNAs) are predicted to regulate up to 90% of the genes in humans, suggesting that they may control every cellular processes in all cells and tissues of the human body! Likely to play a central role in health and disease, a dysfunctional miRNA-based regulation of gene expression may represent the main etiologic factor underlying age-related diseases affecting major organs, such as the brain. Here, we discuss some of the limitations associated to the interpretation and applicability of miRNA data, based on our recent study on the etiology of Alzheimer's disease (AD). Using transiently transfected murine neuronal N2a cells in culture, in parallel to a mouse model of AD, we were able to demonstrate a role for two miRNAs (miR-298 and miR-328) in the regulation of beta-amyloid (Abeta) precursor protein (APP)-converting enzyme (BACE) messenger RNA (mRNA) translation, thereby providing key insights into the molecular basis underlying BACE deregulation in AD. However, whether miRNA data can be extrapolated and transposed to the human context of age-related diseases, such as AD, not only requires caution, but also warrants several considerations.
Highlights
The microRNA-guided RNA silencing pathway is a gene regulatory process present in almost all eukaryotic cells and based on small non-coding RNAs known as miRNAs [1]
Predicted to regulate up to 90% of the genes in humans [2], miRNAs may control every cellular processes in all cells and tissues of the human body! Required for the fine tuning and tight regulation of cellular protein expression, a normal miRNA function is critical for the maintenance of health and prevention of disease [3]
The major research advances pertaining to the possible role and function of miRNAs in neurodegenerative diseases, such as Alzheimer’s disease (AD), has provided novel perspectives to the pathogenesis of increasingly prevalent, age-related diseases in human
Summary
The microRNA (miRNA)-guided RNA silencing pathway is a gene regulatory process present in almost all eukaryotic cells and based on small non-coding RNAs known as miRNAs [1]. Deregulation of protein expression induced by a dysfunctional miRNA-based regulatory system, which may be either global or miRNA-specific in nature, may represent the main etiologic factor underlying age-related diseases, such as Alzheimer’s disease (AD) that affects the brain (Provost, manuscript submitted).
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