Plant foods contain several bioactive compounds, produced via secondary metabolisms as a defense against predation, herbivores, fungal attack, microbial invasion, UV irradiation, and viral infections. Many evidences point to these bioactive compounds as protective molecules active in the prevention of many degenerative diseases in humans. Polyphenols, in particular anthocyanins and flavonoids contained in vegetables, exhibit remarkable antioxidant and anti-inflammatory activities. In this context, the aim of our project is to test the neuroprotective, antioxidant and anti-inflammatory effects of polyphenolic extracts from the model plant Arabidopsis thaliana on animal models of Alzheimer's disease (AD). Extracts from different ecotypes of Arabidopsis plants will be characterized by chromatographic and spectroscopic methods. The biological activity and anti-inflammatory potential of the extracts will be tested in an animal models of AD, i.e. the transgenic TgCRND8 mice. The molecular mechanism underlying the signal transduction pathways activated by polyphenols will be investigated in BV2 cells treated with amyloid beta peptide. These studies will contribute to the elucidation of the role of nutritional therapy in neurodegenerative disease
We consider this project innovative because it will offer a new paradigm for understanding the AD onset and progression. Also, clarifying the effects of complex mixture of polyphenols with possible synergistic activity may shed new light on the role nutritional therapy in neurodegenerative disease. The detailed chromatographic characterization of the extracts will also allow a correlation with the biological activity in order to define a fingerprint of bioactive components in complex mixtures. Disclosing the molecular mechanism of polyphenol action may also provide insights into disease pathway and contribute to identify new pharmacological targets and possible alternative therapeutic interventions.
The project involves different research groups whose scientific expertise spans from biochemistry to molecular biology and pharmaceutical chemistry. They will cooperate to develop this project in a highly synergistic way, each providing its own specific sound experience and capacity, and sharing a series of different techniques and experimental settings to obtain fully integrated information on the therapeutic potential of polyphenols in the treatment of AD. All the methods and techniques are already available and in current use. No major technical pitfalls are expected.