Folate and memantine treatment protected against Ab(25–35) peptide‐induced neuron cytotoxicity

This study was to investigate whether and mechanisms by which folic acid (FS) or/and memantine (MT), a clinical drug for treatment of Alzheimer's disease, protected against amyloid‐β (Aβ)‐induce neurotoxicity. Neuroblastoma cells (SH‐SY5Y) were pre‐incubated with folate or/and MT, and then treated with Aβ (25–35) . Neuronal death and signaling were assayed. Treatment of SH‐SY5Y cells with 50 μM Aβ (25–35) for 48 hrs significantly induced apoptotic and necrotic death, which coincided with elevation of calcium and superoxide levels, increased mitochondrial (mt) membrane depolarization, and cytochrome c release. MT treatment at 20 μM ameliorated depolarized mt membrane potential of Aβ (25–35) ‐treated cells, yet did not affect cell death. FS at 1000 μM, but not 500 μM, significantly reduced Aβ (25–35) ‐promote calcium influx and apoptotic death. FS at 500 μM in combination with MT treatment protected Aβ (25–35) ‐treated cells from mt membrane depolarization, death signal release of cytochrome c and apoptotic death. High levels of FS (1000 μM) in combination with MT treatment further reduced superoxide levels, apoptotic and necrotic death in Aβ (25–35) ‐treated cells. Collectively, FS in combination with MT treatment promoted synergistic effects to protect neuronal cells from Aβ (25–35) ‐induced apoptotic and necrotic death, mediated by amelioration of ROS production and mt‐associated death signaling.