MicroRNA Expressions in the MPTP-induced Parkinson's Disease Model with Special Reference to miR-124

Abstract

Parkinson?s disease (PD) is an incapacitating neurodegenerative disorder affecting around 10 million people worldwide. It is a multifactorial disease caused by a combination of several genetic and environmental factors. MicroRNAs (miRNAs) are short, non-coding RNAs known to play important roles in several cellular processes in healthy and diseased states. Though there have been a few studies on the role of miRNAs in PD, not many have assessed the miRNA changes in the MPTP-induced PD animal model which has served as the gold standard in studying several mechanisms associated with PD. In this study, we used an acute model of MPTP-induced PD mice to analyze the miRNA changes in the substantia nigra (SN) isolated by laser capture microdissection. We have identified several miRNAs being differentially expressed in the PD model. Analysis of PD-specific mRNA expression profile revealed the deregulation of many miRNA-target mRNAs. Among the miRNAs, downregulation of the brain-enriched miR-124 in the SN modulates the expression of the calpain1/cdk5 pathway proteins by targeting calpain1. Our study is the first to analyze miRNA expression changes in the SN of MPTP-induced PD mouse model and provides insight into the role of miRNAs in regulating gene expression in PD.