SASP-Secreted MMP-9 from Senescent Microglia Generates Pathological TDP-43 C-Terminal Fragments That Propagate ALS Pathology

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The hypothesis proposes that MMP-9 (matrix metalloproteinase-9), secreted via the senescence-associated secretory phenotype (SASP) from senescent microglia, generates pathological C-terminal fragments of TARDBP (TDP-43) that propagate ALS pathology through cytoplasmic aggregation seeding. High-strength evidence from TDP-43 ALS mouse models demonstrates that reactive microglia expressing MMP-9 remo