Novel mechanism of regulation of brain plasticity
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This paper deals with the justification of a new hypothesis that in the of transition of NMDA receptors from normal into excitotoxicic functioning the decisive role plays the time coarse of activation of specific MAP kinase, which is sensitive to the extracellulary factors, ERK 1/2 (extracellulary regulated kinase, isoforms 1 and 2). As it is known, specific agonist of these receptors, N-methyl-D-aspartate (NMDA) challenges the short term activation of this kinase, which leads not to the neuronal cell death but to cell adaptation, while the neurotoxin homocysteine under the same conditions induces the long term activation of ERK 1/2 kinase and correspondingly leads to the massive cells death. Intracellular buffer of free radicals, neuropeptide carnosine (β-alanyl-L-histidine) transforms the excitotoxic response of the receptors to homocysteine into the normal one, correspondingly saves the cells from necrotic death. We suppose that the same exitotoxic mechanism takes place during stroke development resulting in neuronal death, and all the substances, which are able to transform MAPK activation from the continuous regime into transitory one, might be considered as effective neuron protectors from the oxidative damage and thus be used in stroke therapy.
Keywordsexcitotoxicity NMDA homocysteine MAPK oxidative stress stroke carnosine
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