IOs, mainly the isoform ASIC1, favor an i.c. excessive accumulation of Na+, Ca++, and H+ in MS and other HNDDs, resulting in severe axonal degeneration and neural damage, secondary to Ca++ overload and acidification-mediated apoptosis. Tissue acidosis further activates ASIC1, which precedes neuroinflammation and other autoimmune phenomena. A decrease in the CNS pHi opens ASIC1, which, through the stimulation of Ca++ into neural cells, induces axonal injury, apoptosis, and demyelination in MS, and β-amyloid accumulation in AD. Here, ASIC1 is linked to Alzheimer disease.