Postsynaptic mechanisms of excitotoxicity: Involvement of postsynaptic density proteins, radicals, and oxidant molecules.
Traditional models of neuronal excitotoxicity focused on the overactivation of receptors such as the ionotropic N-methyl-D-aspartate (NMDA)-subtype glutamate receptor. Recent developments have shifted focus to downstream neurotoxic signaling molecules with exciting implications to specific strategies for treating excitotoxic disorders. This review outlines these developments and introduces newly emerging evidence implicating the involvement of the melastatin subfamily in anoxic neuronal death. Both of these converge on the production of reactive oxygen species (ROS), including superoxide, nitric oxide (NO) and the oxidant peroxynitrite.
Forder
J P
JP
Division of Fundamental Neurobiology, University Health Network, Toronto, Ontario, Canada M5T 2S8.
Tymianski
M
M
D000818:Animals; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000503:physiopathology; D008565:Membrane Proteins / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D009498:Neurotoxins / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000378:metabolism
D005609:Free Radicals; D008565:Membrane Proteins; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human