Circulating miRNA Signatures in Early-Stage Huntington’s Disease

Abstract

Abstract Huntington’s Disease (HD) is a neurodegenerative disorder caused by the expansion of CAG repeats on exon 1 of the huntingtin (htt) gene. This mutation results in the expression of an aberrant protein, mutant HTT, which sets in place a cascade of events that eventually leads to neuronal death within the basal ganglia and cerebral cortex. MicroRNAs (miRNAs) are a class of small non-coding RNAs of 18 - 22 nucleotides long that play important roles in post-transcriptional regulation due to their abilities to interact with the 3'-UTR regions of mRNAs. Though generated in the nucleus, a significant portion of miRNAs are secreted into the plasma as free molecules or in vesicles for intercellular signaling. Those circulating miRNAs may provide a unique opportunity to study important pathophysiological mechanisms in HD in a non-invasive manner due to their resistance to degradation, ease of detection, and their known regulatory roles in response to inflammation and neurodevelopmental disorders. More recent studies have suggested that miRNA could be used in therapeutic applications. In this study, we sought to identify the aberrant expression of specific miRNAs extracted from the plasma of early-stage HD patients. Clinical Trial Registration number: NCT01937923