PRKAA2 and amyotrophic lateral sclerosis: Moreover, AMPK hyper-activation in differentiated primary neurons reduces the number of synapses and leads to a loss of neuronal network functionality (Domise et al., 2019) and AMPK signaling has been associated with amyotrophic lateral sclerosis, neurodegenerative and psychiatric disorders (Perera and Turner, 2016; Rosso et al., 2016).