Dysregulation of MicroRNAs and PIWI-Interacting RNAs in a Parkinson's Disease Model Overexpressing Human α-Synuclein and Influence of .

MicroRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) regulate gene expression and biological processes through specific genetic and epigenetic mechanisms. Recent studies have described a dysregulation of small non-coding RNAs in Parkinson's disease (PD) tissues but have been limited in scope. Here, we extend these studies by comparing the dysregulation of both miRNAs and piRNAs from transgenic () nematodes overexpressing pan-neuronally human α-synuclein wild-type (WT) (HASN OX) or mutant (HASN OX). We observed 32 miRNAs and 112 piRNAs dysregulated in HASN OX compared with WT. Genetic crosses of HASN OX PD animal models with null mutants, the ortholog of TDP-43, an RNA-binding protein aggregated in frontal temporal lobar degeneration, improved their behavioral deficits and changed the number of dysregulated miRNAs to 11 and piRNAs to none. Neuronal function-related genes , , , , and were predicted to be targeted by cel-miR-1018, cel-miR-355-5p ( and ), cel-miR-800-3p, and 21ur-1581 accordingly. This study provides a molecular landscape of small non-coding RNA dysregulation in an animal model that provides insight into the epigenetic changes, molecular processes, and interactions that occur during PD-associated neurodegenerative disorders.