Gandouling protection against brain injury in Wilson's disease via SIRT1/FoxO3

Validation Score: 0.900 Price: $0.50 Hepatolenticular degeneration (Wilson's disease) TX mice (Wilson's disease model), DL mice (control) Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting SIRT1, FoxO3, GPX4, SLC7A11, ACSL4, FTH1, P53 in TX mice (Wilson's disease model), DL mice (control). Primary outcome: Neurological function improvement and reduction of neuronal ferroptosis

Description

This animal model study investigated the neuroprotective mechanism of Gandouling, a Chinese medicine, in hepatolenticular degeneration (Wilson's disease) by examining its effects on the SIRT1/FoxO3 pathway-mediated ferroptosis. TX mice (disease model) were treated with various interventions including Gandouling, resveratrol (SIRT1 activator), and EX-527 (SIRT1 inhibitor) for 4 weeks. The study comprehensively evaluated neurological function through behavioral tests, assessed cellular damage markers including apoptosis and oxidative stress, and measured protein and mRNA expression of key pathway components. The research aimed to demonstrate that Gandouling protects against neuronal damage by inhibiting ferroptosis through modulation of the SIRT1/FoxO3 signaling pathway.

TARGET GENE
SIRT1, FoxO3, GPX4, SLC7A11, ACSL4, FTH1, P53
MODEL SYSTEM
TX mice (Wilson's disease model), DL mice (control)
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
SIRT1/FoxO3 signaling pathway, ferroptosis pathway
SOURCE
extracted_from_pmid_41946579
PRIMARY OUTCOME
Neurological function improvement and reduction of neuronal ferroptosis

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.900 composite

📖 Wiki Pages

SIRT1 ProteinproteinGPX4 Protein - Glutathione Peroxidase 4proteinGPX4 (Glutathione Peroxidase 4)proteinGPX4** is a protein. This page describes its strucredirectFTH1 ProteinproteinFOXO3 ProteinproteinFOXO3 Protein (Forkhead Box O3)proteinFTH1 Protein — Ferritin Heavy ChainproteinACSL4 ProteinproteinACSL4 Inhibition for Ferroptosis Prevention in NeuideaSLC7A11 Gene - xCT Cystine/Glutamate AntiportergeneGPX4 Gene - Glutathione Peroxidase 4geneFTH1 Gene — Ferritin Heavy Chain 1geneFOXO3 GenegeneACSL4 Gene - Acyl-CoA Synthetase Long Chain Familygene

Protocol

TX mice randomly divided into 6 groups: model control, Gandouling, resveratrol, Gandouling+resveratrol, EX-527, and Gandouling+EX-527. DL mice served as blank controls. 4-week treatment intervention followed by behavioral testing (Morris water maze, wire hanging test, pole test), TUNEL assay for apoptosis, DCFH-DA method for ROS measurement, colorimetric assays for Fe²⁺ and MDA levels, immunofluorescence for SIRT1/FoxO3, and Western blotting/qPCR for protein/mRNA expression analysis.

Expected Outcomes

Gandouling treatment would improve neurological function, reduce neuronal apoptosis, decrease oxidative stress markers, and modulate SIRT1/FoxO3 pathway expression to inhibit ferroptosis

Success Criteria

Improved performance in behavioral tests, reduced apoptosis and oxidative stress markers, and favorable modulation of SIRT1/FoxO3 pathway proteins compared to model controls

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