IP: Dr. Mario Ezquerra

Resumen del proyecto: Background: We previously performed a genome-wide DNA array methylation study (450k Human Methylation Array (Illumina)) in induced pluripotent stem cells (iPSC)-derived dopaminergic neurons (DAn) generated from monogenic and sporadic Parkinson disease (PD) patients as well as of healthy subjects. We observed extensive and statistical significant DNA methylation changes in DAn from PD patients. Objective: We aim to clarify the biological significance of PD-DAn alterations, analysing exhaustively the epigenetic alterations present in PD, and research the presence of epigenetic changes in blood cells from PD patients, in order to find common epigenetic changes in both tissues. Methodology: (i) Generation of iPSC-derived DAn model of PD; (ii) Analysis of the DNA methylation by using whole genome bisulphite Sequencing, and histone mark profiles by ChIP-Seq, of the PD iPSC-derived DAn model. (iii) Methylation analysis of specific blood subtypes using the 450k Human Methylation Array (Illumina). Expected results: Using a patient iPSC-derived DAn model of PD we have recently identified late PD-associated spontaneous neural phenotypes of reduced neurite arborization, deficient clearance of autophagic vesicles and SNCA accumulation (published results). These cellular phenotypes were antedated by large early PD-associated epigenetic and expression changes (submitted manuscript). Our study will contribute to understand the possible role of epigenetic alterations on the pathophysiology of PD, and potentially will open a new door for diagnostic or prognostic clinical epigenetic blood biomarkers.

Entidad financiadora: Instituto de Salud Carlos III