Grant: Discovery Grants Program - Individual

Our main research program focuses on the cellular mechanisms underlying neuronal damage in neurodegenerative disorders such as Parkinson's disease. We are analyzing the role of some oxidative and inflammatory agents in cellular degeneration and mortality. In this context, we are also interested in neuroprotective cellular mechanisms, i.e. the possibility that some steroids, particularly phytoestrogens and phytosterols, may act as anti-oxidative and/or anti-inflammatory molecules. Even if oxidative reactions are normal features of cellular metabolism, the production of oxidative molecules can overwhelm cellular anti-oxidative capacity, causing oxidative stress. Recent studies support the existence of a link between oxidative stress and the complex neurodegeneration processes. We have demonstrated that several oxidative toxins such as paraquat and MPTP act as neurodegeneration mediators. Thus, we have evaluated several strategies to protect neurons and prevent neurodegeneration by reducing oxidative stress. Interestingly, phytoestrogens are naturally-occurring molecules that may exert anti-oxidative actions in vivo and in vitro and protect against neurodegenerative diseases without causing secondary hormonal events. Our results show that some phytoestrogens, such as resveratrol, quercetin, and sesamin, reduce neuronal mortality induced by oxidative toxins. In addition, we have demonstrated that these natural occurring molecules can play an important anti-inflammatory role. Finally, our results may open doors to the rational design of neuroprotective anti-oxidant and anti-inflammatory agents with decreased hormonal side effects.