Increased oxidative stress is a widely accepted factor in the development and progression of Alzheimer's disease. Here we introduced alginate - an antioxidant oligosaccharide - as a protective agent on NT2 neural cell line against H2O2/FeSO4-induced cell death. Our results demonstrate that alginate not only protects the neurons against cell death, as measured by MTT test and caspase-3 activity determination, but also decreases amyloid beta formation. In the present study we could induce A beta formation through oxidative stress in NT2 neurons, one of the most appropriate cell line models in Alzheimer's disease and provided the first documentation that alginate can be neuroprotective by suppressing A beta formation. We further showed that alginate exerts its protective effect by up regulation of HO-1, gamma-GCS, Hsp-70, Nrf2 and inhibiting caspase-3 and NF-kappa B. This study raises the possibility of developing alginate as a potential neuroprotective agent. (c) 2009 Elsevier Ltd. All rights reserved.