Therefore, considering that the neuroprotection exerted by SOD1 and ApoSOD1 may pass through a rapid and transient [Ca2+]i increase, in the present study we investigated, by a pharmacological and siRNA approach, the involvement of the Na+/Ca2+ exchanger isoforms (NCXs), the cyclic adenosine diphosphate-ribose (cADPR) receptor and the purinergic receptor P2X7, most of which are implicated in the pathogenesis of ALS. The gene discussed is P2RX7; the disease is amyotrophic lateral sclerosis.