Advances in MicroRNAs and Alzheimer s Disease Research

Molecular and cellular neurobiological studies of the miRNA-mediated gene silencing in Alzheimer's disease represent the exploration of a new frontier of miRNAs biology and the potential development of new diagnostic tests and genetic therapies for this neurodegenerative disease. In few years our understanding of microRNA (miRNA) biogenesis, molecular mechanisms by which miRNAs regulate gene expression, and the functional roles of miRNAs has been expanded. MiRNA are double-stranded RNAs (dsRNAs) ?22 nucleotides in lenght. These small noncoding RNA molecules operate as guides for RISC (RNA Induced Silencing Complex) to cleave a target mRNA in case of a perfect complementarity (siRNA) or to block the target mRNA translation (miRNA) when there is an imperfect pairing between miRNAs and the targets. In mammalian cells the repression of translation by miRNA is mediated by an imperfect pairing with the 3?UTRs of the mRNA targets. Interestingly, numerous miRNAs are expressed in a spatially and temporally controlled manner in the nervous system, suggesting that mRNA post- transcriptional regulation by microRNAs may be particularly relevant in neural development and function. Individual microRNAs can reduce the production of hundred proteins and miRNAs-mediated post-transcriptional regulation is involved in neuronal differentiation, dendritic spine development and synaptic plasticity. Recently expression profiles of miRNA in Alzheimer's disease brain revealed alterations in many indiviual miRNAs and several in vitro and in vivo studies aimed to the exploration of functional role of miRNA in Alzheimer's disease pathogenesis.