Excitatory amino acids and neurotoxicity

In the past three decades evidence indicating a role for excitatory amino acids in determining certain neurological disorders has been accumulated. Although the mechanisms underlying the neuronal damage induced by glutamate are not yet fully understood, many intracellular processes are thought to contribute to the development of excitotoxic injury, acting in combination to determine cell death. In this article we report the leading hypotheses in the understanding of excitatory amino acid-induced toxicity, which focus on the role of Ca²⁺ and Ca²⁺ - activated processes, for example the activation of Ca²⁺ - dependent enzymes such as kinases, lipases and proteases and the formation of the messenger molecule nitric oxide for the production of free radicals, in the development of neuronal damage. The possible implications for excitotoxicity of second messenger systems generated by glutamate acting on the metabotropic receptor subtypes will also be discussed.