Objective: Our study aims to discover and delineate the role of novel long non-coding RNAs (lncRNAs) in Parkinson’s disease (PD).

Background: LncRNAs have been widely known to play important roles in the progression of several debilitating diseases such cancers, cardiovascular and neurological diseases. They can regulate gene expression transcriptionally or post-transcriptionally via several mechanisms. They can also be detected in bodily fluids and be used as biomarkers to improve diagnosis and prognosis of several diseases. Despite recent advances in the field, currently no lncRNA (or RNA) based biomarkers are available for the diagnosis or treatment of PD. In this study, we aim to discover novel lncRNAs possessing biomarker potential and delineate their role in PD.

Method: a. LncRNA candidates were mined using publicly available RNAseq datasets from PD, non- PD and control derived neuron samples.
b. Promising lncRNA candidates were measured using qPCR in SH-SY5Y cells treated with 2mM MPP⁺ for 24 and 48 hours to mimic Parkinsonism.
c. Over-expression experiments for a lncRNA candidate were performed in order to uncover its function during PD pathogenesis via qPCR and western blotting.

Results: a. RNA-seq data illustrated that 10 lncRNA candidates were significantly modulated in PD vs non-PD samples.
b. We tested these candidate lncRNAs in a SH-SY5Y-MPP⁺ model of PD and found that one candidate lncRNA was upregulated, four were significantly downregulated and one was not regulated in SH-SY5Y cells upon MPP⁺ treatment.
c. Over-expression of the most promising candidate, named lncG1, in our PD model led to an increase in the expression of enzymes involved in Dopamine synthesis (Tyrosine Hydroxylase and Dopa Decarboxylase) as well as the proliferation marker, PCNA. Over-expression of lncG1 reversed the negative effects of the neuro-toxin MPP, thus, this lncRNA could have a neuro-protective role in PD.

Conclusion: The present study sheds light on the regulation of lncRNAs in PD. Moreover, our study highlights lncRNAs to be potentially interesting therapeutic targets for PD. Further work is warranted to decipher the biomarker potential and therapeutic value of lncRNAs for PD.

References: 1) Acharya S, Salgado-Somoza A, Stefanizzi FM, Lumley AI, Zhang L, Glaab E, May P, Devaux Y. Non-Coding RNAs in the Brain-Heart Axis: The Case of Parkinson’s Disease. Int J Mol Sci. 2020 Sep 6;21(18):6513. doi: 10.3390/ijms21186513. PMID: 32899928; PMCID: PMC7555192.
2) Woodard CM, Campos BA, Kuo SH, Nirenberg MJ, Nestor MW, Zimmer M, Mosharov EV, Sulzer D, Zhou H, Paull D, Clark L, Schadt EE, Sardi SP, Rubin L, Eggan K, Brock M, Lipnick S, Rao M, Chang S, Li A, Noggle SA. iPSC-derived dopamine neurons reveal differences between monozygotic twins discordant for Parkinson’s disease. Cell Rep. 2014 Nov 20;9(4):1173-82. doi: 10.1016/j.celrep.2014.10.023. Epub 2014 Nov 6. PMID: 25456120; PMCID: PMC4255586.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/long-non-coding-rnas-in-parkinsons-disease-bringing-back-life-to-the-grey-matter/