id_685. DECODING PALMITOYLATION CHANGES IN PARKINSON’S DISEASE FIBROBLASTS
L. Murillo-Hernández1,2,3, L. Muñoz-Delgado2,3,4, P. Mir2,3,4, A. Fontán-Lozano1,2, R. Mejías1,2
1 Department of Physiology, Faculty of Biology, University of Seville, Seville, Spain
2 Movement Disorders Unit, Neurology Service, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, University of Seville, Seville, Spain
3 Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Carlos III Institute of Health, Madrid, Spain
4 Department of Medicine, Faculty of Medicine, University of Seville, Seville, Spain
INTRODUCTION: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the degeneration of the nigrostriatal pathway, which is essential for motor control. S-acylation, also known as protein palmitoylation (PP), is a reversible lipid post-translational modification (PTM) that regulates protein function. A previous pilot study revealed differences in the cortical palmitome of PD patients.
AIM(S): The aim of this study was to characterize the expression and PP levels in dermal fibroblasts from sporadic PD patients compared to controls to identify potential peripheral biomarkers.
METHOD(S): We examined the expression and PP levels of proteins in dermal fibroblasts from sporadic PD patients and controls (n=4-8 per group). Total and palmitoylated proteins were isolated using an acyl-biotin exchange assay (ABE), followed by western blotting and proteomic.
RESULTS: ABE-WB analyses of human fibroblasts suggested potential palmitoylation of the PD-related proteins. Notably, proteomic analyses revealed dysregulation of pathways implicated in PD pathophysiology. Palmitome analysis of the same samples identified 30 differentially palmitoylated proteins (DPPs) in PD patients compared to controls.
CONCLUSIONS: Our findings suggest distinct proteomic and palmitoylation signatures in dermal fibroblasts from sporadic PD patients, supporting the use of this cell model for detecting PD-associated PP alterations, investigating their pathological mechanisms, and facilitating the future development of biomarkers based on this PTM.
FINANCIAL SUPPORT: This work was supported by the Spanish Ministry of Science and Innovation (PID2023-150376OB-I00 - Knowledge Generation Projects 2023). Lucía Murillo is supported by a predoctoral research contract for training of research personnel from the Junta de Andalucía / CUII and the FSE+ (DGP_PRED_2024).