Cerium oxide nanoparticles trigger neuronal survival in a human Alzheimer disease model by modulating BDNF pathway

In engineering and materials science, nanotechnology has made significant advances in the reduction of free radical damage. Despite such advances, there has been little application to biomedical problems. Cross-disciplinary interactions and the application of this technology to biological systems has led to the elucidation of novel nanoparticle antioxidants. Oxidative stress and free radical production are associated with neurodegenerative conditions, including aging, trauma, Alzheimer's and Parkinson's diseases, etc. The antioxidant properties of cerium oxide nanoparticles show promise in the treatment of such diseases. Recent reports suggest that CeO2 and other nanoparticles are potent, and probably regenerative, free radical scavengers in vitro and in vivo. In this work, the effects of CeO2 nanoparticles on an in vitro human AD model are investigated. The validation of new therapeutic agents implies the understanding of their mechanisms of action, therefore the following parameters were investigated under nanoparticles treatment: cell viability, cell death, neurite atrophy, neuronal marker localization and the expression of factors, i.e. PPARß, BDNF, TrkB, involved in the signal transduction pathways of neuronal survival. The data obtained, demonstrate that CeO2 nanoparticles do not act as mere anti-oxidant agents, but they seems to affect, directly or indirectly, signal transduction pathways involved in neuronal death and neuroprotection, raising the possibility of their use as therapeutic tools for neurodegenerative diseases.