P2RX4 and amyotrophic lateral sclerosis: This is likely to be important because an upregulation of surface P2X receptors (in particular P2X4 subtype) was observed in various pathophysiological contexts such as ischemia, chronic pain [23], or neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) or Alzheimer's disease (AD) [38, 65–67].