TG transamidating activity is a downstream target of the ERK pathway. A, TG inhibitors exerted protection when added up to 14–17 h post-glutamate exposure. B–D, Glutamate induces phosphorylated ERK (pERK) (B); MEK inhibitors U0126 and SL327 block pERK activation (B) and protect against glutamate toxicity (C) by reducing TG activation to the control level (D). *p < 0.05; **p < 0.01 compared with glutamate treatment alone; untreated controls are calculated at 100% of survival. U0124 is a negative control for U0126.