ICA1 affects APP processing through the PICK1-PKCα signaling pathway.
CNS Neurosci Ther
; 30(6): e14754, 2024 Jun.
Article
de En
| MEDLINE
| ID: mdl-38884369
ABSTRACT
AIMS:
Islet cell autoantigen 1 (ICA1) is involved in autoimmune diseases and may affect synaptic plasticity as a neurotransmitter. Databases related to Alzheimer's disease (AD) have shown decreased ICA1 expression in patients with AD. However, the role of ICA1 in AD remains unclear. Here, we report that ICA1 expression is decreased in the brains of patients with AD and an AD mouse model.RESULTS:
The ICA1 increased the expression of amyloid precursor protein (APP), disintegrin and metalloprotease 10 (ADAM10), and disintegrin and metalloprotease 17 (ADAM17), but did not affect protein half-life or mRNA levels. Transcriptome sequencing analysis showed that ICA1 regulates the G protein-coupled receptor signaling pathway. The overexpression of ICA1 increased PKCα protein levels and phosphorylation.CONCLUSION:
Our results demonstrated that ICA1 shifts APP processing to non-amyloid pathways by regulating the PICK1-PKCα signaling pathway. Thus, this study suggests that ICA1 is a novel target for the treatment of AD.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Transduction du signal
/
Précurseur de la protéine bêta-amyloïde
/
Protéines du cycle cellulaire
/
Protein kinase C-alpha
/
Maladie d'Alzheimer
Limites:
Animals
/
Female
/
Humans
/
Male
Langue:
En
Journal:
CNS Neurosci Ther
Sujet du journal:
NEUROLOGIA
/
TERAPEUTICA
Année:
2024
Type de document:
Article
Pays de publication:
Royaume-Uni