Transcriptome analysis in LRRK2 and idiopathic Parkinson's disease at different glucose levels
Type-2 diabetes (T2D) and glucose metabolic imbalances have been linked to neurodegenerative diseases, including Parkinson's disease (PD). To detect potential effects of different glucose levels on gene expression, by RNA-seq we analyzed the transcriptome of dermal fibroblasts from idiopathic PD (iPD) patients, LRRK2-associated PD (L2PD) patients, and healthy controls (total n = 21 cell lines), which were cultured at two different glucose concentrations (25 and 5 mM glucose). In PD patients we identified differentially expressed genes (DEGs) that were related to biological processes mainly involving the plasmatic cell membrane, the extracellular matrix, and also neuronal functions. Such pathway deregulation was largely similar in iPD or L2PD fibroblasts. Overall, the gene expression changes detected in this study were associated with PD independently of glucose concentration. ; This work was supported by CIBERNED / Instituto de Salud Carlos III (ISCIII) (grant PIE14/00061) (to M.-J.M.), and the Fondo de Investigaciones Sanitarias from ISCIII (grant PIE20/00259) (to M.E.). R.F.-S. was supported by a Jóvenes Investigadores (JIN) grant of the Spanish Ministry of Economy and Competitiveness (MINECO) and the Agencia Estatal de Investigación (AEI) (AEI/FEDER/UE) (grant #SAF2015-73508-JIN), and a Miguel Servet grant from the Instituto de Salud Carlos III (grant #CP19/00048). A.E-C. was funded by ISCIII /MINECO (PT17/0009/0019) and co-funded by FEDER. M.F. was funded through a María de Maeztu grant (#MDM-2017-0729). IDIBAPS receives funding from the CERCA Program from the Generalitat de Catalunya and the FEDER Program from the European Union.
