Transcriptomics and weighted protein network analyses of the LRRK2 protein interactome reveal distinct molecular signatures for sporadic and LRRK2 Parkinson's Disease.
Journal
NPJ Parkinson's disease
ISSN: 2373-8057
Titre abrégé: NPJ Parkinsons Dis
Pays: United States
ID NLM: 101675390
Informations de publication
Date de publication:
03 Aug 2024
03 Aug 2024
Historique:
received:
12
02
2024
accepted:
24
07
2024
medline:
4
8
2024
pubmed:
4
8
2024
entrez:
3
8
2024
Statut:
epublish
Résumé
Mutations in the LRRK2 gene are the most common genetic cause of familial Parkinson's Disease (LRRK2-PD) and an important risk factor for sporadic PD (sPD). Multiple clinical trials are ongoing to evaluate the benefits associated with the therapeutical reduction of LRRK2 kinase activity. In this study, we described the changes of transcriptomic profiles (whole blood mRNA levels) of LRRK2 protein interactors in sPD and LRRK2-PD cases as compared to healthy controls with the aim of comparing the two PD conditions. We went on to model the protein-protein interaction (PPI) network centred on LRRK2, which was weighted to reflect the transcriptomic changes on expression and co-expression levels of LRRK2 protein interactors. Our results showed that LRRK2 interactors present both similar and distinct alterations in expression levels and co-expression behaviours in the sPD and LRRK2-PD cases; suggesting that, albeit being classified as the same disease based on clinical features, LRRK2-PD and sPD display significant differences from a molecular perspective. Interestingly, the similar changes across the two PD conditions result in decreased connectivity within a topological cluster of the LRRK2 PPI network associated with protein metabolism/biosynthesis and ribosomal metabolism suggesting protein homoeostasis and ribosomal dynamics might be affected in both sporadic and familial PD in comparison with controls.
Identifiants
pubmed: 39097579
doi: 10.1038/s41531-024-00761-8
pii: 10.1038/s41531-024-00761-8
doi:
Types de publication
Journal Article
Langues
eng
Pagination
144Subventions
Organisme : Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation)
ID : MJFF-023427
Organisme : Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation)
ID : MJFF-021335
Organisme : Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation)
ID : MJFF-021335
Organisme : Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation)
ID : MJFF-023427
Informations de copyright
© 2024. The Author(s).
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