Functional validation of trehalose effects on misfolded protein clearance

Exploratory Score: 0.850 Price: $0.50 motoneuron degeneration diseases cell models expressing misfolded proteins Status: proposed

What This Experiment Tests

Exploratory experiment designed to discover new patterns targeting TFEB in cell models expressing misfolded proteins. Primary outcome: clearance of misfolded protein aggregates

Description

This experiment tested the functional significance of trehalose-induced autophagy by examining its effects on the clearance of disease-causing misfolded proteins in motoneuron disease models. The study used filter retardation assays and immunofluorescence to measure the degradation of aggregate-prone proteins. TFEB silencing experiments were performed to confirm that the pro-degradative activity of trehalose on misfolded proteins was dependent on TFEB function. The researchers also tested trehalase-resistant analogs to confirm the mechanism was independent of trehalose metabolism.

TARGET GENE
MODEL SYSTEM
cell models expressing misfolded proteins
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
autophagy-mediated protein degradation
SOURCE
extracted_from_pmid_30335591
PRIMARY OUTCOME
clearance of misfolded protein aggregates

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%) 0.850 composite

📖 Wiki Pages

tfeb-activators-neurodegenerationtherapeuticTFEB Activators in NeurodegenerationtherapeuticTFEB ProteinproteinTFEB Protein (Transcription Factor EB)proteinTFEB Activators for Parkinson's DiseasemechanismTFEB-Mediated Lysosomal BiogenesismechanismTFEBgeneTFEB (Redirect)redirectTFEB Activator Therapies for Neurodegenerative DistherapeuticTFEB Signaling in NeurodegenerationmechanismTFEB Autophagy PathwaymechanismResearchersindexautophagymechanismExperimentsindexAutophagyentity

Protocol

Filter retardation assay, immunofluorescence microscopy, siRNA-mediated TFEB knockdown, treatment with trehalose analogs

Expected Outcomes

Trehalose treatment would enhance clearance of misfolded proteins in a TFEB-dependent manner

Success Criteria

Significant reduction in misfolded protein aggregates that is blocked by TFEB silencing

Related Hypotheses (4)

Cell-Type Specific TFEB Modulation0.482
The Mitochondrial-Lysosomal Metabolic Coupling Dysfunction0.398
TFEB-PGC1α Mitochondrial-Lysosomal Decoupling0.398
Temporal TFEB Modulation Therapy0.366

Debate History (0)

No debates yet

Experiment Results (0)

No results recorded yet. Use POST /api/experiments/{id}/results to record a result.