Trehalose-induced lysosomal membrane permeabilization and TFEB activation

Exploratory Score: 0.900 Price: $0.50 motoneuron degeneration NSC34 neuroblastoma cells Status: proposed

What This Experiment Tests

Exploratory experiment designed to discover new patterns targeting TFEB in NSC34 neuroblastoma cells. Primary outcome: TFEB nuclear translocation and autophagy gene upregulation

Description

This experiment investigated the mechanism by which trehalose induces autophagy in neuronal cell models. The study examined trehalose-mediated lysosomal enlargement and membrane permeabilization (LMP), leading to calcium-dependent phosphatase PPP3/calcineurin activation, TFEB dephosphorylation and nuclear translocation. The researchers used multiple cell lines including NSC34 neuroblastoma cells and demonstrated that trehalose upregulates genes for lysosomal components and autophagy-related proteins in a PPP3- and TFEB-dependent manner. The study also tested trehalase-resistant analogs like melibiose and lactulose to confirm the mechanism is independent of trehalose metabolism.

TARGET GENE
MODEL SYSTEM
NSC34 neuroblastoma cells
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
autophagy-lysosomal pathway
SOURCE
extracted_from_pmid_30335591
PRIMARY OUTCOME
TFEB nuclear translocation and autophagy gene upregulation

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

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Protocol

Cell culture treatment with trehalose and analogs, immunofluorescence microscopy, western blotting, RT-qPCR, lysosomal membrane permeabilization assays, calcium imaging, siRNA knockdown studies

Expected Outcomes

Trehalose treatment would induce lysosomal membrane permeabilization, activate calcineurin, promote TFEB nuclear translocation, and upregulate autophagy genes

Success Criteria

Significant increase in TFEB nuclear localization, upregulation of autophagy-related genes, and enhanced clearance of misfolded proteins

Related Hypotheses (4)

Cell-Type Specific TFEB Modulation0.677
The Mitochondrial-Lysosomal Metabolic Coupling Dysfunction0.652
TFEB-PGC1α Mitochondrial-Lysosomal Decoupling0.622
Temporal TFEB Modulation Therapy0.609

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