Resolve: TFEB/TFE3 Parallel Activation Drives Coordinated Organelle Clearance via CLEAR Network

Falsifiable prediction from high-scoring hypothesis (score=0.727, gene=TFEB (TFEB), TFE3 (TFE3)). Hypothesis: Does parallel activation of TFEB and TFE3 synergistically enhance lysosomal and mitochondrial biogenesis through the CLEAR network, providing superior proteostasis restoration vs single-TFEB approaches? Success criteria: 1. Dual TFEB/TFE3 activation (via novel small-molecule or AAV-TFEB/TFE3) increases expression of >15 CLEAR network genes by >2-fold in iPSC-derived neurons. 2. Lysosomal activity (Cathepsin B/V) increases by >50% vs single-TFEB activation. 3. Mitochondrial function (OCR) improves by >30% and mitochondrial ROS decreases by >40%. 4. In neurodegeneration models: alpha-synuclein aggregation decreases by >40% vs single-TFEB or vehicle control.

$750
OPEN
Confidence:
70%
Created: 2026-04-28

Linked Targets (1)

TFEB TFEB Protein PDB:5HQB0.34
🧬 View 3D Structure — PDB 5HQB click to expand

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Detected Targets:
TFEB

3D Protein Structure

View 3D structure: TFEB — PDB 4NTI

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

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Linked Hypotheses (1)

TFEB/TFE3 Parallel Activation Drives Coordinated Organelle Clearance via CLEAR N TFEB (TFEB), TFE3 (TFE3), mTOR0.73