Cervilla-Martínez, J. F., Rodríguez-Gotor, J. J., Wypijewski, K. J., Fontán-Lozano, Á., Wang, T., Santamaría, E., Fuller, W. and Mejías, R. (2022) Altered cortical palmitoylation induces widespread molecular disturbances in Parkinson's disease. International Journal of Molecular Sciences, 23(22), 14018. (doi: 10.3390/ijms232214018) (PMID:36430497) (PMCID:PMC9696982)
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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, to better understand the role of protein palmitoylation in PD and the pathways altered in this disease, we analyzed the differential palmitoyl proteome (palmitome) in the cerebral cortex of PD patients compared to controls (n = 4 per group). Data-mining of the cortical palmitome from PD patients and controls allowed us 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 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 suggests 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.
Item Type: | Articles |
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Additional Information: | This work was partially funded by NIH (R21NS085358). JJRG had an Erasmus+ fellowship from an EU programme for education, training, youth, and sport. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Fuller, Professor Will and Wypijewski, Mr Krzysztof |
Creator Roles: | Wypijewski, K.Methodology, Investigation, Writing – original draft Fuller, W.Conceptualization, Data curation, Methodology, Investigation, Writing – original draft |
Authors: | Cervilla-Martínez, J. F., Rodríguez-Gotor, J. J., Wypijewski, K. J., Fontán-Lozano, Á., Wang, T., Santamaría, E., Fuller, W., and Mejías, R. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | International Journal of Molecular Sciences |
Publisher: | MDPI |
ISSN: | 1661-6596 |
ISSN (Online): | 1422-0067 |
Copyright Holders: | Copyright © 2022 The Authors |
First Published: | First published in International Journal of Molecular Sciences 23(22):14018 |
Publisher Policy: | Reproduced under a Creative Commons License |
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