The Impact of Dysregulated microRNA Biogenesis Machinery and microRNA Sorting on Neurodegenerative Diseases

Abstract

MicroRNAs (miRNAs) are 22-nucleotide noncoding RNAs involved in the differentiation, development, and function of cells in the body by targeting the 3′- untranslated regions (UTR) of mRNAs for degradation or translational inhibition. miRNAs not only affect gene expression inside the cells but also, when sorted into exosomes, systemically mediate the communication between different types of cells. Neurodegenerative diseases (NDs) are age-associated, chronic neurological diseases characterized by the aggregation of misfolded proteins, which results in the progressive degeneration of selected neuronal population(s). The dysregulation of biogenesis and/or sorting of miRNAs into exosomes was reported in several NDs, including Huntington’s disease (HD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease (AD). Many studies support the possible roles of dysregulated miRNAs in NDs as biomarkers and therapeutic treatments. Understanding the molecular mechanisms underlying the dysregulated miRNAs in NDs is therefore timely and important for the development of diagnostic and therapeutic interventions. In this review, we focus on the dysregulated miRNA machinery and the role of RNA-binding proteins (RBPs) in NDs. The tools that are available to identify the target miRNA-mRNA axes in NDs in an unbiased manner are also discussed.