Investigación | Proyectos Financiados

STUDIO DI BIOMARCATORI PER PATOLOGIE NEURODEGENERATIVE

Studio di biomarcatori per patologie neurodegenerativeNeurodegenerative diseases (ND) are debilitating and largely untreatable conditions that are strongly linked with age. Amongst these disorders, the dementias are responsible for the greatest burden of disease, with Alzheimer’s disease and related disorders affecting some 7 million people in Europe. The current costs of the order of €130 billion per annum to care for people with dementia across Europe highlight age-related neurodegenerative disease as one of the largest medical and societal challenges faced by our society. PD is the second most common neurodegenerative disorder worldwide after AD. Objective of the present project is the design of moleules able to catch potential neurodegenerative biomarkers. Ultimately, these will be used to functionalize ultra–small Magnetic Nanoparticles (MNPs) for the early and ultrasensitive realization of a diagnostic device based on magnetoresistive sensors, microfluidic device, Specifically we plan to selectively functionalize nanoparticles using the following protocols:1. Aptamer functionalization. Specific aptameric peptide sequences will be defined based on NMR conformational data and molecular dynamic simulation procedures. Selected sequences will be synthesised and tested for their binding affinity to purified target biomarkers as both soluble molecules and when covalently bound to the surface of MNP. 2.Antibody functionalization. Antibodies specific for the target proteins will be tested as such and after the isolation of their light chains. The use of antibody light chain fragments will ensure a powerful alternative to the aptamer approach. 3.Molecular imprinting. The field of molecularly imprinted polymers (MIP) is a very rapidly evolving field including the development of MIP selective for protein ligands. Molecular imprinting of polymers with target macromolecules will be pursued during the deposition of the polymer shell on the MNP. Sophisticated computational approaches based on coarse-grained molecular dynamics techniques will provide a design platform that takes into account both polymer surface properties and protein conformational features.1.Randino R, Grimaldi M, Persico M, De Santis A, Cini E, Cabri W, Riva A, D'Errico G, Fattorusso C, D'Ursi AM*, Rodriquez M*. Sci Rep. 2016 Dec 22;6:38846. doi: 10.1038/srep38846. IF 4.2592.Bruno A, Scrima M, Novellino E, D'Errico G, D'Ursi AM*, Limongelli V. Sci Rep. 2015 Mar 17;5:9200. doi: 10.1038/srep09200. IF 4.2593.Scrima M, Lauro G, Grimaldi M, Di Marino S, Tosco A, Picardi P, Gazzerro P, Riccio R, Novellino E, Bifulco M, Bifulco G, D'Ursi AM*. J Med Chem. 2014 Sep 25;57(18):7798-803. doi: 10.1021/jm500869x. IF 6.2594.Grimaldi M, Marino SD, Florenzano F, Ciotta MT, Nori SL, Rodriquez M, Sorrentino G, D'Ursi AM*, Scrima M. Future Med Chem. 2016 Jul;8(11):1179-89. doi: 10.4155/fmc-2016-0006.. IF 3.5565.Rodriquez M, Cretoso DS, Euterpio MA, Russo P, Crescenzi C, Aquino RP. Anal Bioanal Chem. 2015 Oct;407(25):7691-701. doi: 10.1007/s00216-015-8933-6. IF 3.436.Marzolla V, Armani A, Feraco A, De Martino MU, Fabbri A, Rosano G, Caprio M. Steroids. 2014 Dec;91:46-53. doi: 10.1016/j.steroids.2014.05.001 IF. 2.727.Testa C, Scrima M, Grimaldi M, D'Ursi AM, Dirain ML, Lubin-Germain N, Singh A, Haskell-Luevano C, Chorev Rovero P, Papini AM. J Med Chem. 2014 Nov 26;57(22):9424-34. doi: 10.1021/jm501027w. IF 6.259