cGAS/STING pathway validation in TDP-43 mutant mice

Validation Score: 0.850 Price: $0.50 Amyotrophic Lateral Sclerosis TDP-43 mutant mice Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting TARDBP in TDP-43 mutant mice. Primary outcome: Prevention of NF-κB and type I IFN upregulation

Description

Validation study using TDP-43 mutant mice to confirm the role of cGAS/STING signaling in TDP-43-associated neuroinflammation. The experiment involved pharmacologic inhibition or genetic deletion of cGAS and STING components to assess their impact on NF-κB and type I interferon upregulation induced by TDP-43 mutations. This in vivo model provided crucial evidence that the cGAS/STING pathway is a key mediator of TDP-43-driven neuroinflammation in the context of a whole organism with intact immune and nervous systems.

TARGET GENE

TARDBP (Score: 0.514)

MODEL SYSTEM

TDP-43 mutant mice

ESTIMATED COST

TIMELINE

0 months

PATHWAY

cGAS/STING, NF-κB, type I interferon pathways

SOURCE

extracted_from_pmid_33031745

PRIMARY OUTCOME

Prevention of NF-κB and type I IFN upregulation

Scoring Dimensions

📖 Wiki Pages

TARDBP/TDP-43 Proteinprotein TARDBP Protein (TDP-43)protein TARDBP Mutations in Amyotrophic Lateral Sclerosisdisease TARDBP — TAR DNA Binding Protein 43gene TDP-43 Aggregate Neuronscell TDP-43 (TAR DNA-Binding Protein 43) - Biomarkerbiomarker TDP-43 Splicing Modulation Therapyidea TDP-43 Proteinopathy Neuronsredirect TDP-43 vs Tau Pathology Determination in GRN vs MAgeneral TDP-43 PET Ligand Development for FTD and ALSexperiment Amyotrophic Lateral Sclerosisredirect STING Genegene TDP-43 Proteinopathy Neuronscell TDP-43 Pathology in Corticobasal Syndromedisease TDP-43 Proteinopathy Neurons in Frontotemporal Demcell

Protocol

TDP-43 mutant mouse generation, cGAS/STING inhibition via pharmacologic or genetic approaches, inflammatory marker analysis, behavioral and pathological assessments

Expected Outcomes

cGAS/STING inhibition should prevent TDP-43-induced neuroinflammatory responses and potentially ameliorate disease progression

Success Criteria

Significant reduction in inflammatory markers and improved neurological outcomes with cGAS/STING pathway inhibition

Related Hypotheses (5)

Cryptic Exon Silencing Restoration0.703

Cross-Seeding Prevention Strategy0.689

RNA-Binding Competition Therapy for TDP-43 Cross-Seeding0.642

Glycine-Rich Domain Competitive Inhibition0.640

Glial Neuroinflammatory Amplification by TDP-43 Pathology0.680

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