Searching for MIND: microRNAs in neurodegenerative diseases

Abstract

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. Interestingly, numerous miRNAs are expressed in a spatially and temporally controlled manner in the nervous system, suggesting that their posttrascriptional regulation may be particularly relevant in neural development and function. MiRNA studies in neurobiology showed their involvement in synaptic plasticity and brain diseases. In this review ,correlations between miRNA-mediated gene silencing and Alzheimer's, Parkinson's, and other neurodegenerative diseases will be discussed. Molecular and cellular neurobiological studies of the miRNAs in neurodegeneration represent the exploration of a new Frontier of miRNAs biology and the potential development of new diagnostic tests and genetic therapies for neurodegenerative diseases.

Figure 1

APP or BACE1 upregulation might lead to Aβ overproduction in Alzheimer's Disease. The picture shows molecular pathways modulating APP and BACE1 expression and amyloidogenic processing of APP by BACE1 and the γ-secretase complex leading to Aβ production. Reduction of miRNA/RISC posttranscriptional regulation of APP and/or BACE1 mRNA induces the increase of the relative proteins, which drive to Aβ accumulation. Changes of miRNA expression might trigger molecular events inducing AD pathology or generate a feed-forward mechanism during AD progression (as suggested for miR-298 and miR-328).