Detection, visualization and quantification of protein complexes in human Alzheimer's disease brains using proximity ligation assay.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
24 07 2023
24 07 2023
Historique:
received:
06
03
2023
accepted:
30
06
2023
medline:
27
7
2023
pubmed:
25
7
2023
entrez:
24
7
2023
Statut:
epublish
Résumé
Examination of healthy and diseased human brain is essential to translational neuroscience. Protein-protein interactions play a pivotal role in physiological and pathological processes, but their detection is difficult, especially in aged and fixed human brain tissue. We used the in-situ proximity ligation assay (PLA) to broaden the range of molecular interactions assessable in-situ in the human neuropathology. We adapted fluorescent in-situ PLA to detect ubiquitin-modified proteins in human brains with Alzheimer's disease (AD), including approaches for the management of autofluorescence and quantification using a high-content image analysis system. We confirmed that phosphorylated microtubule-associated protein tau (Serine202, Threonine205) aggregates were modified by ubiquitin and that phospho-tau-ubiquitin complexes were increased in hippocampal and frontal cortex regions in AD compared to non-AD brains. Overall, we refined PLA for use in human neuropathology, which has revealed a profound change in the distribution of ubiquitin in AD brain and its association with characteristic tau pathologies.
Identifiants
pubmed: 37488165
doi: 10.1038/s41598-023-38000-4
pii: 10.1038/s41598-023-38000-4
pmc: PMC10366145
doi:
Substances chimiques
tau Proteins
0
Ubiquitin
0
Ubiquitinated Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
11948Subventions
Organisme : NIA NIH HHS
ID : R01 AG078803
Pays : United States
Organisme : NIA NIH HHS
ID : K76 AG060001
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR027396
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023. The Author(s).
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