Pathogenic microRNAs common to brain and retinal degeneration; recent observations in Alzheimer's disease and age-related macular degeneration

Abstract

MicroRNAs (miRNAs), ~22 nt single-stranded non-coding RNAs (ncRNAs) abundant in the human brain and retina, have emerged as significant post-transcriptional regulators of messenger RNA (mRNA) abundance and complexity in the human central nervous system (CNS) in aging, health, and disease. Of the 2050 different miRNAs in the human body so far identified, only about 25-30 are abundant in either the brain or the retina, underscoring the high selection pressure carried by RNA sequences located within these select ncRNAs (1-7). It is noteworthy to point out that: (i) that brain neocortex and retina share a common neuroectodermal origin; (ii) that brain and retina share a subfamily of specific miRNA species; and (iii) that the multilayered assemblies of both neural and retinal cells are targeted by pathogenic processes that drive progressive pro-inflammatory neurodegeneration (5-9). Indeed, pathologically up-regulated miRNAs common to both the prototypic age-related inflammatory degeneration of the brain in Alzheimer's disease (AD) and of the retina in age-related macular degeneration (AMD) appear to be associated with deficits in the expression of messenger RNA (mRNA) and gene families involved in the innate-immune response, inflammation, neurotrophism, synaptogenesis, and amyloidogenesis (Figure 1). In this "Opinion" paper for the Frontiers in Neurology Special Research Topic, we will highlight some of the most recent work in this research area, with emphasis on a family of five up-regulated pro-inflammatory miRNAs - miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a, and miRNA-155-that are emerging as key mechanistic contributors to the AD and AMD process.