Altered cortical palmitoylation induces widespread molecular disturbances in Parkinson's disease
Fecha
2022Autor
Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión publicada / Argitaratu den bertsioa
Impacto
|
10.3390/ijms232214018
Resumen
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 th ...
[++]
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. [--]
Materias
Cerebral cortex,
Interactome,
Palmitoylation,
Parkinson´s disease,
Proteomics
Editor
MDPI
Publicado en
International Journal of Molecular Sciences, 2022, 23(22), 1-18
Departamento
Universidad Pública de Navarra. Departamento de Ciencias de la Salud /
Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila
Versión del editor
Entidades Financiadoras
This work was partially funded by NIH (R21NS085358). JJRG had an Erasmus+ fellowship from an EU programme for education, training, youth, and sport. The Brain and Body Donation Program is supported by the National Institute on Aging (P30 AG19610 Arizona Alzheimer’s Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer’s Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson’s Disease Consortium)