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: 0.510)

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/TDP-43 Proteinprotein TARDBP Protein (TDP-43)protein TARDBP — TAR DNA Binding Protein 43gene TARDBP Mutations in Amyotrophic Lateral Sclerosisdisease DNA Repair Therapy for Neurodegenerationtherapeutic DNA Damage Repair Therapy for Neurodegenerationtherapeutic TDP-43 Proteinredirect TDP-43 Proteinprotein TDP-43 Proteinprotein TDP-43 Proteinredirect DNA-PKcs (PRKDC) Proteinprotein DNA Ligase IV Proteinprotein DNA Ligase III Proteinprotein TDP-43 RNA Granule Pathwaymechanism TDP-43 DNA Repair Mechanism in ALS and Dementiamechanism

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 (4)

Cryptic Exon Silencing Restoration0.462

Cross-Seeding Prevention Strategy0.451

Glycine-Rich Domain Competitive Inhibition0.429

RNA-Binding Competition Therapy for TDP-43 Cross-Seeding0.374

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