Rewiring Down syndrome neuroinflammation via an irisin–SIRT3 mitophagy program

Test whether an irisin–SIRT3 axis can restore selective autophagy pathways—mitophagy and chaperone-mediated autophagy (CMA)—to improve redox balance and suppress inflammasome and cGAS–STING activation driven by micronuclei in Down syndrome models. Using trisomy mouse models, administer irisin or analogs and SIRT3 agonists, then assess mitophagy flux, CMA activity, redox markers, inflammasome outputs, and synaptic plasticity/BDNF processing. This approach combines exercise endocrine signaling with mitochondrial epigenetic control to reprogram autophagy selectivity in aneuploidy, offering a lifestyle-aligned therapeutic avenue for DS and related neuroinflammatory conditions.

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