AhR agonist effects on NEP in APP/PS1 mice

Validation Score: 0.900 Price: $0.50 Alzheimer's disease APP/PS1 mice Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting NEP in APP/PS1 mice. Primary outcome: NEP expression and enzyme activity

Description

In vivo study using APP/PS1 transgenic mice to investigate the effects of AhR agonists on NEP expression and enzyme activity. The experiment tested the same AhR ligands used in the cell culture studies (L-Kynurenine, FICZ, diosmin, and indole-3-carbinol) in a well-established mouse model of Alzheimer's disease. This study aimed to validate the cellular findings in a more physiologically relevant system and determine if AhR activation could have therapeutic potential for Alzheimer's disease through enhanced Aβ clearance mechanisms.

TARGET GENE
NEP
MODEL SYSTEM
APP/PS1 mice
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
AhR signaling pathway
SOURCE
extracted_from_pmid_34522212
PRIMARY OUTCOME
NEP expression and enzyme activity

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

APP ProteinproteinAPP/PS1 Dual Transgenic Mouse ModelmodelAPP/PS1 Double Transgenic Mouse ModelmechanismAPP Processing and Amyloid-Beta ProductionmechanismAPP-BACE1-Fe65 ComplexmechanismAPP Amyloid Pathway in Alzheimer's DiseasemechanismAPP→Amyloid-beta→Plaque→Alzheimer's Disease CausalpathwayAPP Gene Dosage Reduction Therapy for Down SyndromideaAPP — Amyloid Precursor ProteingeneAPP GenegeneAPP Swedish Mutation (APPswe)mutationAPP Flemish Mutation (APP Flemish)diseaseAPP Dutch Mutation (APP Dutch)diseaseAPP Arctic Mutation (APP Arctic)diseaseAPP-Overexpressing Neuronscell

Protocol

Western blotting, immunofluorescence, quantitative RT-PCR and enzyme activity assay in APP/PS1 mice treated with AhR agonists

Expected Outcomes

AhR agonists would increase NEP expression and enzyme activity in vivo

Success Criteria

Significant increase in NEP expression and enzyme activity in brain tissue

Related Hypotheses (0)

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