Effect of nanocompounds on the modulation of adenosine and metabotropic glutamate receptors, on different in vitro models

  1. Giust, Davide
Dirigida por:
  1. José Luis Albasanz Herrero Director/a
  2. Mairena Martin Lopez Director/a

Universidad de defensa: Universidad de Castilla-La Mancha

Fecha de defensa: 25 de junio de 2010

Tribunal:
  1. Juan Emilio Feliu Albiñana Presidente/a
  2. Inmaculada Ballesteros Yáñez Secretario/a
  3. Jesús Pintor Vocal
  4. Marta Barrachina Castillo Vocal
  5. Davide Bonifazi Vocal

Tipo: Tesis

Resumen

Engineering compounds and materials for interfacing with biology and medicine is actually one of the most interesting challenge of scientists from different areas. In that sense, one of the investigated compounds due to their possible applications in a variety of areas, have been fullerenes and allotropic carbon made related compounds, like nanotubes and nanohorns. The large number of possible applications of this family compounds, in particular [60]fullerenes, is strictly related to the peculiar physical and chemical properties of their unsaturated carbon structures, although implicating a low solubility in the majority of organic solvent, and only partial solubility in aqueous systems, and for that reason demonstrating toxic effects in vivo, due to the accumulation in tissues. The most used strategies used to bypass these limitations, have been the modification of the main structure with appendages which increasing the solubility in aqueous solvent, including biological fluids. In the present study we used an hydrosoluble derivative of [60]fullerene bis-adduct trans-3 isomer, demonstrating to own a large number of possible biological applications, from HIV-protease inhibition, antitumor activity, to antibacterial activity. We tested it on different in vitro models of neurodegenerative diseases. Furthermore, we tested [60]fullerenes as different gold modified surfaces, to proof biocompatibility and eventually effect of modified surface. The context we used to test [60]fullerene, has been about the neurodegenerative disease, as Alzheimer's disease. In these diseases have been study the relevant role of L-Glutamate and amyloid-beta peptide as responsible of an irreversible degeneration of neuronal cells in CNS (central nervous system). Furthermore as investigated by our group, adenosine receptors and metabotropic glutamate receptors seem to have differential role in neurodegeneration and/or neuroprotection of neuronal cells exposed L-Glu and Aß toxicity. The modulation of these receptors have been demonstrated to be a promising target to engineering new therapeutics compound for neurodegenerative disease, in that sense [60]fullerene hydrosoluble derivative has proved its habylity to modulate the expression of adenosine and metabotropic glutamate receptors in these models. Furthermore the protective effect of [60]fullerene is preserved also as modified surfaces (SAMs), and demonstrating to be totally biocompatible to biological model used.