Interpretation and applicability of microrna datato the context of Alzheimer's and age-related diseases

Abstract

Generated by the ribonuclease III Dicer, microRNAs (miRNAs) are predicted to regulate up to 90% of the genes inhumans, suggesting that they may control every cellular processes in all cells and tissues of the human body! Likely to playa central role in health and disease, a dysfunctional miRNA-based regulation of gene expression may represent the mainetiologic factor underlying age-related diseases affecting major organs, such as the brain. Here, we discuss some of thelimitations associated to the interpretation and applicability of miRNA data, based on our recent study on the etiology ofAlzheimer's disease (AD). Using transiently transfected murine neuronal N2a cells in culture, in parallel to a mouse modelof AD, we were able to demonstrate a role for two miRNAs (miR-298 and miR-328) in the regulation of β-amyloid (Aß)precursor protein (APP)-converting enzyme (BACE) messenger RNA (mRNA) translation, thereby providing key insights intothe molecular basis underlying BACE deregulation in AD. However, whether miRNA data can be extrapolated andtransposed to the human context of age-related diseases, such as AD, not only requires caution, but also warrants severalconsiderations. © Provost.