The neuroprotective effect of agmatine against amyloid β-induced apoptosis in primary cultured hippocampal cells involving ERK, Akt/GSK-3β, and TNF-α.

β-Amyloid peptide (Aβ), the major element of senile plaques in Alzheimer's disease (AD), has been found to accumulate in brain regions critical for memory and cognition. Deposits of Aβ trigger neurotoxic events which lead to neural apoptotic death. The present study examined whether agmatine, an endogenous polyamine formed by the decarboxylation of L-arginine, possesses a neuroprotective effect against Aβ-induced toxicity. Primary rat hippocampal cells extracted from the brains of 18-19-day-old embryos were exposed to 10 µM of Aβ (25-35) in the absence or presence of agmatine at 150 or 250 µM. Additionally, the involvement of Akt (Protein Kinae B), GSK-3β (glycogen synthase kinase 3-β), ERK (Extracellular Signal-Regulated Kinase) and TNF-α (Tumor necrosis factor-α) in the agmatine protection against Aβ-induced neurotoxicity was investigated. Agmatine significantly prevented the effect of Aβ exposure on cell viability and caspase-3 assays. Furthermore, agmatine considerably restored Aβ-induced decline of phospho-Akt and phospho-GSK and blocked Aβ-induced increase of phospho-ERK and TNF-alpha. Taken together, these findings might shed light on the protective effect of agmatine as a potential therapeutic agent for AD.