Trehalose-induced lysosomal changes and TFEB activation

Exploratory Score: 0.900 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: TFEB nuclear translocation and lysosomal membrane permeabilization

Description

This experiment investigated the mechanism by which trehalose induces autophagy in cellular models of motoneuron degeneration. The study demonstrated that trehalose causes rapid and transient lysosomal enlargement and membrane permeabilization (LMP), which correlates with calcium-dependent phosphatase PPP3/calcineurin activation, leading to TFEB dephosphorylation and nuclear translocation. The researchers used immunofluorescence microscopy to track lysosomal changes and TFEB subcellular localization, and performed biochemical assays to measure phosphatase activity and protein modifications.

TARGET GENE
MODEL SYSTEM
NSC34 neuroblastoma x spinal cord cells
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
autophagy/lysosome pathway
SOURCE
extracted_from_pmid_30335591
PRIMARY OUTCOME
TFEB nuclear translocation and lysosomal membrane permeabilization

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

AtlasX Biocompanytfeb-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 PathwaymechanismResearchersindexautophagymechanismAutophagyentity

Protocol

Cells treated with trehalose, followed by immunofluorescence analysis for TFEB localization and lysosomal markers, biochemical assays for PPP3/calcineurin activity, and measurement of lysosomal membrane integrity

Expected Outcomes

Trehalose treatment should induce lysosomal changes leading to TFEB activation and autophagy upregulation

Success Criteria

Significant TFEB nuclear translocation, lysosomal enlargement, and increased autophagy gene expression

Related Hypotheses (4)

Cell-Type Specific TFEB Modulation0.559
The Mitochondrial-Lysosomal Metabolic Coupling Dysfunction0.471
TFEB-PGC1α Mitochondrial-Lysosomal Decoupling0.458
Temporal TFEB Modulation Therapy0.440

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