🧫 Experiment Protocol
ValidationAmyotrophic Lateral SclerosisTARDBPTDP-43 mutant miceproposed
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.
PRIMARY OUTCOME
Prevention of NF-κB and type I IFN upregulation
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
PROTOCOL
TDP-43 mutant mouse generation, cGAS/STING inhibition via pharmacologic or genetic approaches, inflammatory marker analysis, behavioral and pathological assessments