TARDBP and infection: Unclear; Key mechanisms include TDP-43 misfolding and aggregation, mitochondrial dysfunction, oxidative stress, impairment of protein clearance, defective RNA processing, glutamate excitotoxicity, glial dysfunction, nucleocytoplasmic transport defects, axonal transport disruption, impaired DNA repair, and neuroinflammation. Infections with pathogens (e.g., EV or HIV) can trigger TDP-43 upregulation or aggregation (95, 96). These cause progressive degeneration and loss of motor neurons (97).