Abstract
Parkinson's disease (PD) represents a significant global health challenge influenced by environmental factors and the accumulation of alpha-synuclein. MicroRNAs (miRNAs), crucial regulators of gene expression, play pivotal roles in neurodegenerative processes. This study is structured into two primary investigations. Firstly, miRNA microarray analysis in Caenorhabditis elegans treated with mouse 2.5 S-NGF and custom peptide (HNP) revealed distinct expression profiles, notably upregulating miR-1-3p and miR-255-3p compared to controls. Pathway analysis implicated these miRNAs in neuroprotective mechanisms, including PI3K, Wnt/β-catenin, and TGF signalling, while downregulated miRNAs were associated with apoptosis, p53, and innate immunity pathways. These results underscore the neuroprotective roles of NGF and HNP through miRNA-mediated mechanisms in C. elegans. Secondly, a comparative analysis of global miRNA profiles between paraquat-induced PD model worms and NGF/HNP-treated worms identified novel miRNAs and revealed inverse expression patterns indicative of miRNA profile restoration by NGF/HNP pre-treatment. Principal component and correlation analyses demonstrated distinct miRNA regulation profiles across treatments. Gene network analysis identified target mRNAs involved in diverse cellular processes, highlighting potential therapeutic roles of NGF and HNP in neurodegenerative diseases like Parkinson's, mainly through regulation of miR-4813-3p associated with α-synuclein clearance. These findings underscore the promise of NGF and HNP as therapeutic strategies targeting neurodegenerative mechanisms mediated by miRNAs.