TRPV1 alleviates APOE4-dependent microglial antigen presentation and T cell infiltration in Alzheimer's disease.
APOE4
Cholesterol
Microglia
TRPV1
Tau
Journal
Translational neurodegeneration
ISSN: 2047-9158
Titre abrégé: Transl Neurodegener
Pays: England
ID NLM: 101591861
Informations de publication
Date de publication:
29 Oct 2024
29 Oct 2024
Historique:
received:
28
06
2024
accepted:
17
09
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
Persistent innate and adaptive immune responses in the brain contribute to the progression of Alzheimer's disease (AD). APOE4, the most important genetic risk factor for sporadic AD, encodes apolipoprotein E4, which by itself is a potent modulator of immune response. However, little is known about the immune hub that governs the crosstalk between the nervous and the adaptive immune systems. Transient receptor potential vanilloid type 1 (TRPV1) channel is a ligand-gated, nonselective cation channel with Ca Using Ca Both APOE4 microglia derived from induced pluripotent stem cells of AD patients and APOE4-related tauopathy mouse model showed significantly increased cholesterol biosynthesis and accumulation compared to their APOE3 counterparts. Further, cholesterol dysregulation was associated with persistent activation of microglia and elevation of major histocompatibility complex II-dependent antigen presentation in microglia, subsequently accompanied by T cell infiltration. In addition, TRPV1-mediated transient Ca The findings provide new perspectives for the treatment of APOE4-dependent neurodegeneration including AD.
Sections du résumé
BACKGROUND
BACKGROUND
Persistent innate and adaptive immune responses in the brain contribute to the progression of Alzheimer's disease (AD). APOE4, the most important genetic risk factor for sporadic AD, encodes apolipoprotein E4, which by itself is a potent modulator of immune response. However, little is known about the immune hub that governs the crosstalk between the nervous and the adaptive immune systems. Transient receptor potential vanilloid type 1 (TRPV1) channel is a ligand-gated, nonselective cation channel with Ca
METHODS
METHODS
Using Ca
RESULTS
RESULTS
Both APOE4 microglia derived from induced pluripotent stem cells of AD patients and APOE4-related tauopathy mouse model showed significantly increased cholesterol biosynthesis and accumulation compared to their APOE3 counterparts. Further, cholesterol dysregulation was associated with persistent activation of microglia and elevation of major histocompatibility complex II-dependent antigen presentation in microglia, subsequently accompanied by T cell infiltration. In addition, TRPV1-mediated transient Ca
CONCLUSIONS
CONCLUSIONS
The findings provide new perspectives for the treatment of APOE4-dependent neurodegeneration including AD.
Identifiants
pubmed: 39468688
doi: 10.1186/s40035-024-00445-6
pii: 10.1186/s40035-024-00445-6
doi:
Substances chimiques
Apolipoprotein E4
0
TRPV Cation Channels
0
TRPV1 protein, mouse
0
TRPV1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
52Subventions
Organisme : National Natural Science Foundation of China
ID : 82173791
Organisme : Science and Technology Commission of Shanghai Municipality
ID : 23ZR1436600
Informations de copyright
© 2024. The Author(s).
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