Regarding motoneuron diseases (MND), the Sig-1R agonist PRE-084 has shown positive effects reducing the MN death in vitro in organotypic culture of spinal cord subjected to excitotoxic damage (Guzmán-Lenis et al., 2009) and in vivo in the SOD1G93A murine model of ALS (Mancuso et al., 2012), in the wobbler mouse model of spontaneous MN degeneration (Peviani et al., 2014), and after spinal nerve injury in adult mice and rats (Gaja-Capdevila et al., 2021; Penas et al., 2011). Here, SIGMAR1 is linked to mild neurocognitive disorder.