Cytoplasmic HDAC4 recovers synaptic function in the 3×Tg mouse model of Alzheimer's disease.
Alzheimer's disease
SUMOylation
histone deacetylases
neuropathology
synapse
Journal
Neuropathology and applied neurobiology
ISSN: 1365-2990
Titre abrégé: Neuropathol Appl Neurobiol
Pays: England
ID NLM: 7609829
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
revised:
26
08
2022
received:
24
05
2022
accepted:
02
10
2022
pubmed:
5
11
2022
medline:
3
3
2023
entrez:
4
11
2022
Statut:
ppublish
Résumé
Early dysfunction in Alzheimer's disease (AD) is characterised by alterations of synapse structure and function leading to dysmorphic neurites, decreased spine density, impaired synaptic plasticity and cognitive deficits. The class II member HDAC4, which recently emerged as a crucial factor in shaping synaptic plasticity and memory, was found to be altered in AD. We investigated how the modulation of HDAC4 may contribute to counteracting AD pathogenesis. Using a cytoplasmic HDAC4 mutant (HDAC4 Here, we report that in wild-type mice, HDAC4 is localised at synapses and interacts with postsynaptic proteins, whereas in the 3×Tg-AD, it undergoes nuclear import, reducing its interaction with synaptic proteins. Of note, HDAC4 delocalisation was induced by both amyloid-β and tau accumulation. Overexpression of the HDAC4 These results highlight a new role of cytoplasmic HDAC4 in providing a structural and enzymatic regulation of postsynaptic proteins. Our findings suggest that controlling HDAC4 localisation may represent a promising strategy to rescue synaptic function in AD, potentially leading to memory improvement.
Identifiants
pubmed: 36331820
doi: 10.1111/nan.12861
pmc: PMC10099707
doi:
Substances chimiques
Amyloid beta-Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12861Informations de copyright
© 2022 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.
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