Beyond the critical point: An overview of excitotoxicity, calcium overload and the downstream consequences

Neurosci Lett. 2018 Jan 10;663:79-85. doi: 10.1016/j.neulet.2017.08.048. Epub 2017 Aug 24.


Over the past several decades, an overwhelming body of research has greatly expanded our understanding of the mechanisms underlying excitotoxicity in brain ischemia as well as in many chronic neurodegenerative diseases. The identification of an array of molecular targets has opened avenues for neuroprotective strategies and, consequently, has sparked considerable interest for their attractive therapeutic means as pharmacological options. The purpose of this work is to provide a general overview of neuronal excitotoxicity and the inevitable downstream consequences of Ca2+ overload. We also discuss the contribution of Ca2+ transporters in excitotoxicity. This article is part of a Special Issue entitled "Calcium Pumps and Exchangers in Neuronal Injury and Neurodegeneration".

Keywords: Calcium; Calpains; Excitotoxicity; Mitochondria; Na(+)/Ca(2+) exchanger (NCX).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calpain / metabolism*
  • Humans
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Plasma Membrane Calcium-Transporting ATPases / metabolism*
  • Sodium-Calcium Exchanger / metabolism*


  • Sodium-Calcium Exchanger
  • Calpain
  • Plasma Membrane Calcium-Transporting ATPases
  • Calcium