Triggering of Major Brain Disorders by Protons and ATP: The Role of ASICs and P2X Receptors

Neurosci Bull. 2023 May;39(5):845-862. doi: 10.1007/s12264-022-00986-8. Epub 2022 Nov 29.

Abstract

Adenosine triphosphate (ATP) is well-known as a universal source of energy in living cells. Less known is that this molecule has a variety of important signaling functions: it activates a variety of specific metabotropic (P2Y) and ionotropic (P2X) receptors in neuronal and non-neuronal cell membranes. So, a wide variety of signaling functions well fits the ubiquitous presence of ATP in the tissues. Even more ubiquitous are protons. Apart from the unspecific interaction of protons with any protein, many physiological processes are affected by protons acting on specific ionotropic receptors-acid-sensing ion channels (ASICs). Both protons (acidification) and ATP are locally elevated in various pathological states. Using these fundamentally important molecules as agonists, ASICs and P2X receptors signal a variety of major brain pathologies. Here we briefly outline the physiological roles of ASICs and P2X receptors, focusing on the brain pathologies involving these receptors.

Keywords: ASICs; Chronic pain; Epilepsy; Neurodegenerative; P2X receptors; Psychiatric diseases; Stroke.

Publication types

  • Review

MeSH terms

  • Acid Sensing Ion Channel Blockers / pharmacology
  • Acid Sensing Ion Channels* / metabolism
  • Adenosine Triphosphate* / metabolism
  • Alzheimer Disease
  • Amyotrophic Lateral Sclerosis
  • Animals
  • Brain Diseases* / epidemiology
  • Brain Diseases* / metabolism
  • Brain Diseases* / pathology
  • COVID-19
  • Chronic Pain
  • Epilepsy
  • Humans
  • Huntington Disease
  • Ischemic Stroke
  • Mental Disorders
  • Multiple Sclerosis
  • Neurodegenerative Diseases
  • Neuroinflammatory Diseases
  • Parkinson Disease
  • Protons*
  • Receptors, Purinergic P2X* / metabolism

Substances

  • Acid Sensing Ion Channel Blockers
  • Acid Sensing Ion Channels
  • Adenosine Triphosphate
  • Protons
  • Receptors, Purinergic P2X