Note however that the magnitude of the excitotoxic lesion may be a determining factor as to whether upregulation of calpastatin gene transcription through endogenous signaling pathways can proceed and provide a neuroprotective effect, as we found no evidence that this gene is modulated in the brain of APPPS1/SWE mice despite the presence of senile plaques (Laflamme, Rivest, unpublished observation). This evidence concerns the gene CAST and Senile plaques.