TDP-43 mitochondrial invasion and DNA release via mPTP

Exploratory Score: 0.900 Price: $0.50 amyotrophic lateral sclerosis cultured cells Status: proposed

What This Experiment Tests

Exploratory experiment designed to discover new patterns targeting TARDBP in cultured cells. Primary outcome: mitochondrial DNA release

Description

Investigation of how TDP-43 protein invades mitochondria and triggers mitochondrial DNA (mtDNA) release through the mitochondrial permeability transition pore (mPTP). The study examined the mechanism by which cytoplasmic TDP-43 accumulation leads to mitochondrial dysfunction and subsequent mtDNA release into the cytoplasm, which then activates innate immune signaling pathways.

TARGET GENE

TARDBP (Score: 0.514)

MODEL SYSTEM

cultured cells

ESTIMATED COST

TIMELINE

0 months

PATHWAY

mitochondrial permeability transition pore

SOURCE

extracted_from_pmid_33031745

PRIMARY OUTCOME

mitochondrial DNA release

Scoring Dimensions

📖 Wiki Pages

TARDBP — TAR DNA Binding Protein 43gene TARDBP Mutations in Amyotrophic Lateral Sclerosisdisease TARDBP Protein (TDP-43)protein TARDBP/TDP-43 Proteinprotein TDP-43 Pathology in Corticobasal Syndromedisease DNA Methylationentity DNA Damage Repair Deficiency Validation Study in Pexperiment TDP-43 Proteinopathy Neurons in Frontotemporal Demcell DNA Methylation Biomarkers in Neurodegenerationbiomarker Amyotrophic Lateral Sclerosisredirect TDP-43 Aggregate Neuronscell DNA Damage-Accumulating Neurons in Neurodegeneraticell TDP-43 Proteinopathy Neuronscell DNA Damage Response in Corticobasal Syndromemechanism DNA Damage and Repair in Neuronscell

Protocol

Assessment of TDP-43 localization to mitochondria, measurement of mitochondrial permeability transition pore opening, and detection of cytoplasmic mtDNA release

Expected Outcomes

TDP-43 invasion of mitochondria triggers mPTP opening and subsequent mtDNA release

Success Criteria

Detection of mtDNA in cytoplasm following TDP-43 mitochondrial invasion

Related Hypotheses (7)

Cross-Seeding Prevention Strategy0.689

Glycine-Rich Domain Competitive Inhibition0.640

Cryptic Exon Silencing Restoration0.531

RNA-Binding Competition Therapy for TDP-43 Cross-Seeding0.465

STMN2 Cryptic Exon Inclusion is the Earliest Loss-of-Function Marker of TDP-43 Nuclear Depletion in 0.702

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