TARDBP and Alzheimer disease: For example, accumulation of phosphorylated MAPK/ERK Kinase (MEK) and abnormal activation of ERK were detected in AD patients [21, 22]; phosphorylated ERK1/2 was found in the central nervous system (CNS) of ALS patients and mouse models [23, 24]; MEK could phosphorylate TDP-43 upon heat shock, which reduced the RNA binding affinity and altered TDP-43-regulated RNA splicing [25]; and inhibition of p38 was reported to suppress TDP-43-induced neurodegeneration in a fly model of ALS [26].