TFEB silencing and misfolded protein degradation

Exploratory Score: 0.880 Price: $0.50 motoneuron degeneration NSC34 neuroblastoma x spinal cord cells Status: proposed

What This Experiment Tests

Exploratory experiment designed to discover new patterns targeting TFEB in NSC34 neuroblastoma x spinal cord cells. Primary outcome: misfolded protein clearance

Description

This experiment tested the functional importance of TFEB in trehalose-mediated clearance of misfolded proteins associated with motoneuron diseases. The researchers used siRNA to silence TFEB expression and then measured the ability of trehalose to promote degradation of disease-causing misfolded proteins. This approach directly tested whether TFEB is required for the neuroprotective effects of trehalose in models of motoneuron degeneration.

TARGET GENE
MODEL SYSTEM
NSC34 neuroblastoma x spinal cord cells
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
protein quality control/autophagy
SOURCE
extracted_from_pmid_30335591
PRIMARY OUTCOME
misfolded protein clearance

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%) 0.880 composite

Protocol

TFEB silencing using siRNA followed by trehalose treatment and measurement of misfolded protein levels using filter retardation assay and immunoblotting

Expected Outcomes

TFEB silencing should counteract trehalose's ability to promote misfolded protein degradation

Success Criteria

Significant reduction in trehalose's pro-degradative activity when TFEB is silenced

Related Hypotheses (4)

Cell-Type Specific TFEB Modulation0.652
The Mitochondrial-Lysosomal Metabolic Coupling Dysfunction0.627
TFEB-PGC1α Mitochondrial-Lysosomal Decoupling0.597
Temporal TFEB Modulation Therapy0.584

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