Parkinson's disease neurons exhibit alterations in mitochondrial quality control proteins.
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:
08 Aug 2023
08 Aug 2023
Historique:
received:
13
02
2023
accepted:
21
07
2023
medline:
9
8
2023
pubmed:
9
8
2023
entrez:
8
8
2023
Statut:
epublish
Résumé
Mitochondrial dysfunction has been suggested to contribute to Parkinson's disease pathogenesis, though an understanding of the extent or exact mechanism of this contribution remains elusive. This has been complicated by challenging nature of pathway-based analysis and an inability simultaneously study multiple related proteins within human brain tissue. We used imaging mass cytometry (IMC) to overcome these challenges, measuring multiple protein targets, whilst retaining the spatial relationship between targets in post-mortem midbrain sections. We used IMC to simultaneously interrogate subunits of the mitochondrial oxidative phosphorylation complexes, and several key signalling pathways important for mitochondrial homoeostasis, in a large cohort of PD patient and control cases. We revealed a generalised and synergistic reduction in mitochondrial quality control proteins in dopaminergic neurons from Parkinson's patients. Further, protein-protein abundance relationships appeared significantly different between PD and disease control tissue. Our data showed a significant reduction in the abundance of PINK1, Parkin and phosphorylated ubiquitin
Identifiants
pubmed: 37553379
doi: 10.1038/s41531-023-00564-3
pii: 10.1038/s41531-023-00564-3
pmc: PMC10409763
doi:
Types de publication
Journal Article
Langues
eng
Pagination
120Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© 2023. Springer Nature Limited.
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