SASP-Secreted MMP-9 from Senescent Microglia Disrupts Nuclear-Cytoplasmic Transport Leading to TDP-43 Mislocalization and ALS Pathology

h-var-37240814a5

This hypothesis proposes that MMP-9 secreted by senescent microglia in the SASP drives ALS pathology through disruption of nuclear-cytoplasmic transport rather than direct proteolytic cleavage of TDP-43. MMP-9 degrades components of the nuclear pore complex, particularly nucleoporins such as NUP62 and NUP88, which are essential for maintaining the nuclear-cytoplasmic transport machinery. This prot