Together, our data support that the set of reactive astrocyte markers largely identified in ALS models [20,36,40,43] is successfully normalized by the pre-miR-146a regulation, contributing to the recovery of the neuroprotective phenotype of ALS iAstrocytes—despite the effect being exerted by different pathological signaling pathways—thus supporting the distinct reactive signatures in mSOD1-ALS2 and sALS7 samples. Here, ALS2 is linked to amyotrophic lateral sclerosis.