hnRNP A1, hnRNP A2B1, and hnRNP K are dysregulated in tauopathies, but do not colocalize with tau pathology.
RNA binding proteins
hnRNP
neuropathology
phosphorylated tau
tauopathy
Journal
Brain pathology (Zurich, Switzerland)
ISSN: 1750-3639
Titre abrégé: Brain Pathol
Pays: Switzerland
ID NLM: 9216781
Informations de publication
Date de publication:
01 Oct 2024
01 Oct 2024
Historique:
received:
03
04
2024
accepted:
30
08
2024
medline:
2
10
2024
pubmed:
2
10
2024
entrez:
2
10
2024
Statut:
aheadofprint
Résumé
Tau interacts with multiple heterogeneous nuclear ribonucleoproteins (hnRNPs)-a family of RNA binding proteins that regulate multiple known cellular functions, including mRNA splicing, mRNA transport, and translation regulation. We have previously demonstrated particularly significant interactions between phosphorylated tau and three hnRNPs (hnRNP A1, hnRNP A2B1, and hnRNP K). Although multiple hnRNPs have been previously implicated in tauopathies, knowledge of whether these hnRNPs colocalize with tau aggregates or show cellular mislocalization in disease is limited. Here, we performed a neuropathological study examining the colocalization between hnRNP A1, hnRNP A2B1, hnRNP K, and phosphorylated tau in two brain regions (hippocampus and frontal cortex) in six disease groups (Alzheimer's disease, mild cognitive impairment, progressive supranuclear palsy, corticobasal degeneration, Pick's disease, and controls). Contrary to expectations, hnRNP A1, hnRNP A2B1, and hnRNP K did not colocalize with AT8-immunoreactive phosphorylated tau pathology in any of the tauopathies examined. However, we did observe significant cellular mislocalization of hnRNP A1, hnRNP A2B1 and hnRNP K in tauopathies, with unique patterns of mislocalization observed for each hnRNP. These data point to broad dysregulation of hnRNP A1, A2B1 and K across tauopathies with implications for disease processes and RNA regulation.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13305Subventions
Organisme : Faculty of Medicine and Health, University of Sydney
Organisme : Bluesand Foundation
Organisme : Alzheimer's Association
ID : AARG-21-852072
Pays : United States
Organisme : TDM Foundation
Organisme : NIH HHS
ID : P01AG060882
Pays : United States
Organisme : NIH HHS
ID : P30AG066512
Pays : United States
Organisme : National Health and Medical Research Council
ID : 1176607
Organisme : The University of Sydney
Informations de copyright
© 2024 The Author(s). Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.
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