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TDP-43 mitochondrial invasion and mtDNA release in iPSC motor neurons

active
experiment Created: 2026-04-06T12:28:40 By: etl-v1-backfill Quality: 50% ✓ SciDEX ID: exp-aaf75848-e1d3-41b1-b131-3e2c13730e9c
🧫 Experiment Protocol ExploratoryAmyotrophic Lateral SclerosisTARDBPiPSC-derived motor neuronsproposed
Investigation of how cytoplasmic TDP-43 invades mitochondria and triggers mitochondrial DNA (mtDNA) release through the mitochondrial permeability transition pore (mPTP) in induced pluripotent stem cell-derived motor neurons. The study examined the mechanism by which TDP-43 accumulation leads to mitochondrial dysfunction and subsequent DNA release into the cytoplasm, which then activates the cGAS/STING innate immune pathway. This cellular model allowed detailed mechanistic investigation of the molecular events linking TDP-43 pathology to neuroinflammation in ALS.
PRIMARY OUTCOME
Mitochondrial DNA release and cGAS/STING activation
EXPECTED OUTCOMES
TDP-43 invasion into mitochondria should trigger mtDNA release via mPTP opening, leading to cGAS activation and downstream inflammatory signaling
SUCCESS CRITERIA
Demonstration of TDP-43 mitochondrial localization, mtDNA release, and cGAS/STING pathway activation
PROTOCOL
iPSC differentiation to motor neurons, TDP-43 overexpression or mutation, mitochondrial imaging, DNA release assays, cGAS/STING pathway analysis
🧫 Experiment Extras
PATHWAY
cGAS/STING innate immunity pathway
MARKET PRICE
$0.50
STATUS
proposed
Related Target
TARDBPcomposite 0.514
Metadataorigin_type: v1_polymorphic_backfill
origin_typev1_polymorphic_backfill
source_tableexperiments
_schema_version1
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
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Outgoing
0
0 supporting 0 contradicting 0 neutral
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