Ferulic Acid: a Natural Antioxidant Against Oxidative Stress Induced by Oligomeric A-beta on Sea Urchin Embryo

Abstract. Alzheimer's disease (AD) is a progressive, neurodegenerative disorder, characterized by loss of memory and impairment of multiple cognitive functions. Amyloid beta peptide (A) is the main component of amyloid plaques observed in the brain of individuals affected by AD. Oxidative stress and mitochondrial dysfunction, induced by A, are among the earliest events in AD, triggering neuronal degeneration and cell death. Use of natural molecules with antioxidant properties could be a suitable strategy for inhibiting the cell death cascade. Here, by employing the sea urchin Paracentrotus lividus as a model system, and A oligomers, we tested the effectiveness of ferulic acid (FA), a natural antioxidant, as a putative AD neuroprotective compound. By microscopic inspection we observed that FA is able to reverse morphological defects induced by A oligomers in P. lividus embryos. In addition, FA is able to neutralize reactive oxygen species (ROS), recover mitochondrial membrane potential, and block apoptotic pathways. Moreover, this model system has allowed us to obtain information about down- or up-regulation of some key molecules--Foxo3a, ERK, and p53--involved in the antioxidant mechanism.