Altered Cortical Palmitoylation Induces Widespread Molecular Disturbances in Parkinson’s Disease
Year: 2022
Type: article
Study design: Observational Study
Abstract: The relationship between Parkinson's disease (PD), the second most common neurodegenerative disease after Alzheimer's disease, and palmitoylation, a post-translational lipid modification, is not well understood. In this study, we have analyzed the differential palmitome present in the cerebral cortex of PD patients compared to controls (n=4 per group) to better understand the role of protein palmitoylation in PD and the pathways altered in this disease. Data-mining of the cortical palmitome from PD patients and controls has allowed to: i) detect a set of 150 proteins with altered palmitoylation in PD subjects in comparison with controls, ii) describe the biological pathways and targets predicted to be altered by these palmitoylation changes, and iii) depict the overlap between the differential palmitome identified in our study with protein interactomes of the PD-linked proteins α-synuclein, LRRK2, DJ-1, PINK1, GBA and UCHL1. In summary, we have partially characterized the altered palmitome in the cortex of PD patients which is predicted to impact cytoskeleton, mitochondrial and fibrinogen functions, as well as cell survival. Our study points out that protein palmitoylation could have a role in the pathophysiology of PD, and that comprehensive palmitoyl-proteomics offers a powerful approach for elucidating novel cellular pathways modulated in this neurodegenerative disease.
Institutions: Universidad de Sevilla, Instituto de Neurociencias, University of Dundee, University of Glasgow, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Johns Hopkins University, Johns Hopkins Medicine, Universidad Pública de Navarra (UPNA), Navarre Institute of Health Research, Navarrabiomed
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,408
Awards: G1052080286, G1315589061, Inhibitory G protein S-acylation as a therapeutic target in heart failure, G1606131442, G2161113364, G250893170, G2898431357, G3228411741, G3250808129, G3521153818, G3540482749, G3687506083, G6030318873, G6125194395, Arizona Alzheimer's Disease Core Center, G7161884846, G7887587830, G7924111682, G837617365, G9000159448, G9000168263, G961669115
OpenAlex ID: W4309008585