Resolve: mTORC1-TFEB Lysosomal Signaling Axis for Autophagy Restoration

The mTORC1-TFEB axis controls autophagy capacity. In aging neurons, chronic mTORC1 activation keeps TFEB cytoplasmic, impairing lysosomal biogenesis and autophagic clearance. Strategies to displace mTORC1 from the lysosomal surface (Ragulator disruption, AMPK activation) could restore TFEB nuclear translocation. This challenge asks whether this intervention is sufficient to clear pathological aggregates. Falsifiable prediction: Ragulator inhibition in iPSC-derived neurons from LRRK2-G2019S patients should increase LC3-II flux by ≥3-fold and reduce SNCA aggregate area by ≥40% within 72h.

$500
OPEN
Confidence:
62%
Created: 2026-04-28

Linked Targets (2)

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

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SNCA Synuclein alpha PDB:1XQ80.60
🧬 View 3D Structure — PDB 1XQ8 click to expand

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Detected Targets:
TFEBLRRK2SNCA

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)

mTORC1 Displacement from Lysosomal Membrane Enables TFEB Nuclear Translocation a MTOR,RPTOR,TFEB,RragA,RragC,GA0.64