GDP dissociation inhibitor 1 (GDI1) attenuates β-amyloid-induced neurotoxicity in Alzheimer's diseases

Copyright © 2023 Elsevier B.V. All rights reserved..

OBJECTIVE: β-Amyloid (Aβ) induced neurotoxicity is an implicated mechanism in Alzheimer's disease (AD). This study focused on the role of GDP dissociation inhibitor 1 (GDI1) in Aβ-induced neurotoxicity.

METHODS: Data from the GEO database for AD-related datasets GSE140829, GSE63061, GSE36980, and GSE60360 were downloaded and identified common differentially expressed genes (coDEGs). The mRNA levels of GDI1 in the serum of AD patients were analyzed by RT-qPCR. ROC curve evaluated the diagnostic value. Aβ25-35 induced SH-SY5Y cells to construct an AD cell model. CCK-8, flow cytometry, and ELISA assay were used to analyze cell viability, apoptosis, and concentrations of inflammatory factors. KEGG enrichment was employed to analyze the signal pathway of targets from GDI1 in the AD.

RESULTS: The GEO database identifies coDEGs including GDI1. GDI1 is generally elevated in serum from AD patients as well as in Aβ-induced SH-SY5Y cells. GDI1 has 77.97% sensitivity and 84.44% specificity to identify AD patients from controls. Aβ induced decreased cell viability, increased apoptosis, and promoted over-secretion of inflammatory cytokines, but they were all partially weakened by reduced GDI1. What's more, the GDI1 interacting gene and AD target gene were co-enriched on Endocytosis and MAPK signaling pathway.

CONCLUSION: Elevated GDI1 is a potential diagnostic biomarker for AD and that inhibition of GDI1 attenuates Aβ-induced neurotoxicity in AD. Our study offers new horizons for AD treatment.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

2023

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:818

Enthalten in:

Neuroscience letters - 818(2023) vom: 01. Jan., Seite 137564

Sprache:

Englisch

Beteiligte Personen:

Liu, Lina [VerfasserIn]
Liu, Luran [VerfasserIn]
Lu, Yunting [VerfasserIn]
Zhang, Tianyuan [VerfasserIn]
Zhao, Wenting [VerfasserIn]

Links:

Volltext

Themen:

AD
APP protein, human
Amyloid beta-Peptides
GDI1
GDP dissociation inhibitor 1
Guanine Nucleotide Dissociation Inhibitors
Journal Article
Neurotoxicity
Peptide Fragments

Anmerkungen:

Date Completed 21.12.2023

Date Revised 21.12.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.neulet.2023.137564

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM365043036