Present results showed that oral administration of perampanel, a selective, non-competitive AMPA receptor antagonist26, 27, to the AR2H and AR2 mice for 14 days effectively normalized TDP-43 pathology in motor neurons and that its administration for 90 days significantly prevented the progression of the ALS phenotype and the TDP-43 pathology-associated death of motor neurons. Here, TARDBP is linked to amyotrophic lateral sclerosis.