Dysregulation of long non-coding RNAs in neuroinflammation: characterization of LINC00520 and its possible role in Parkinson's disease

Parkinson’s disease (PD) is a widely spread neurodegenerative disorder caused by both genetic and environmental factors, leading to the appearance of characteristic motor and non-motor symptoms. Activated microglia plays a pivotal role in the pathogenesis of PD, sustaining inflammatory processes at the level of neurodegenerative regions by releasing Reactive Oxygen and Nitrogen Species, exposing neurons to oxidative stress. It has recently been observed that the dysregulation of long non-coding RNAs (lncRNAs) could affect the modulation of microglial phenotype in neurodegenerative diseases. Interestingly, we identified a differential expression of some lncRNAs by comparing transcriptomic data of PD patient's vs control brain samples through a detailed meta-analysis. Our study aims to characterize the expression and function of LINC00520, a lncRNA not previously linked to PD, in several PD models. In particular, we tested its gene expression compared to a control lncRNA, LINC00674, in human neuroblastoma SH-SY5Y cells subjected to 6-OHDA treatment and in human monocytic THP-1 cells differentiated towards microglial fate with PMA and stimulated with LPS. We then enrolled the human microglia cell line HMC3 treated with IFN-γ boosted by glucose, to promote the NF-κB inflammatory pathway, or 6-OHDA. The results show a significant upregulation of LINC00520 both in inflammatory states and in oxidative stress conditions. Moreover, preliminary data of RNAi assays against LINC00520 suggested its involvement in oxidative stress-related pathways. Characterization of ZFLNCG09760, a putative LINC00520 ortholog in zebrafish, as an in vivo model, is currently ongoing.