LONG NONCODING RNAs IN TISSUE REPAIR

Parkinsonian disorders are considered the second most common neurological disease in humans. Currently more than 1.2 million peoples across Europe have Parkinson disease (PD). In Luxembourg, PD is the second most common neurodegenerative disease which affects 1200 cases with confirmed diagnosis. Although one of the most recognizable symptoms is the presence of tremors, there are others like bradykinesia and other non-motor symptomssuch as the accumulation of an aberrant form of alpha-synuclein or loss of dopaminergic neurones. Despite significant advances in the treatment of PD, a better understanding of the mechanisms leading to PD is needed to allow developing novel more efficient drugs. Also, novel biomarkers are needed to improve the diagnosis and stratification of PD patients, and to implement personalized healthcare.
Long noncoding RNAs (lncRNAs) are a class of RNA molecules greater than 200 nucleotides in length with little or no protein coding potential. LncRNAs can alter the transcriptome of cells via epigenetic modulations. However, the potential of lncRNAs to diagnose, stratify or treat PD remains unknown. We hypothesized that lncRNAs are deregulated in the early onset of PD and are involved in disease progression. Own recent work identified lncRNAs associated with tissue repair and regulated in neurons. Thus, the overall purpose of this project is to achieve a better characterization of the role of lncRNAs in PD progression, as well as to define their value as biomarkers. The role of lncRNAs will be investigated in the neuronal cell line SH-SY5Y and in induced pluripotent stem cell (iPSC) - derived neurones. We will address the function of lncRNAs via loss- and gain-of-function approaches and we will take advantage of the Luxembourg HELP-PD study, a nation-wide, observational, longitudinal-prospective study for lncRNA biomarker analysis. Expected results include the identification of novel biomarkers and/or therapeutic targets for the treatment of PD.