Characterization of the lncRNA LINC00520 in the developing and adult central nervous system and its correlation to neurodegenerative processes

Understanding the mechanisms underlying human brain development and its dysfunctions has always been challenging due to the involvement of complex and dynamically regulated processes. Over the last few years, long non-coding RNAs (lncRNAs) have emerged as new players in fundamental biological processes, specifically in CNS development, neuronal proliferation, differentiation, homeostasis and synaptic plasticity. Given their importance, even a slight alteration in their expression levels has been linked to a wide range of neurological disorders, including Parkinson's disease (PD). Notably, by comparing the transcriptome of brain samples from PD patients and controls, we were able to determine that the expression of several lncRNAs, previously unrelated to the disease, was altered. We focused on LINC00520, since it was one of the most significantly up-regulated. To better define its physiopathological role, we employed several human in vitro models, ranging from neuronal to microglial cell lines. More specifically, SH-SY5Y, THP-1 and HMC3 cell lines were treated with different compounds (6-OHDA, Rotenone, LPS, IFN glucose) to induce oxidative and inflammatory stress responses and mimic PD conditions. Additionally, we performed RNAi assays directed against LINC00520 using the same experimental settings. Upon treatments, silencing or the combination of the two, our analyses revealed fluctuations in the expression levels of specific stress-related markers depending on LINC00520 modulation. An accurate examination of genomic traits neighbouring LINC00520 led to the identification of a syntenic region on Zebrafish chromosome 17, harbouring LOC100535512 as a potential orthologue. Interestingly, gene expression studies on Zebrafish embryos and adult tissues suggest a meaningful role of the lncRNA, especially during the gastrulation period and in the adult CNS.