We found that in silico predicted combinations formed by Alitretinoin and Pranlukast (CD1) or Alitretinoin and Mefloquine (CD2) exerted effective neuroprotection in an in vitro model of ALS by reducing the toxic effects of chronic excitotoxicity on both microglia reactivity and MN survival. This evidence concerns the gene CD2 and amyotrophic lateral sclerosis.