Ricerc@Sapienza

Amyloid proteins (APs) and related diseases (e.g. Alzheimer disease and ßA) are among the hot topics of the last decades. This proteins are substantially harmless in their native state, whereas in their misfolded state they show strong aggregation tendencies that lead to formation amyloid fibrils. It's commonly accepted that the harmful species are the prefibrillar oligomers (PFOs) interacting with neuronal membranes. Going deeply, it seems from many recent works that this interaction is localized on the so-called "lipid-rafts" (LRfs), which catalyze the aggregation of APs.

To investigate the interaction mechanisms between PFOs and LRfs, the first part of the project involves the characterization of calcitonin PFOs in solution, with and without liposomes (LPs). The latter exhibit different degree of LRfs mimesis, with particular attention to charged components of the LRfs such as monogangliosides-GM1 or other components affecting LP structure such as cholesterol. The study of the interaction mechanisms of the systems is carried out, at molecular level, by spectroscopy (UV-vis, FT-IR and FS) microscopy (AFM, FE-SEM, EF-TEM), DLS and Laungmuir trough techniques, to identify the toxic structure among the aggregates.

The last part involves the development of gold nanoparticles (AuNPs) as delivers of drug able to inactivate the toxic specie identified in the first part of the project. Size-controlled (5-10 nm) AuNPs will be synthetized with mixed pH-sensitive biocompatible organic thiols (e.g. 4-mercaptobenzoic acid, pMBA, and 2-diethylaminoethanethiol, DEA). The AuNPs will be loaded with molecules capable to disrupt amyloid aggregates (e.g. EPPS) or exhibiting anti-inflammatory properties (e.g. Curcumin).
These systems will be also studied coupled with transferrin, a plasma protein capable to cross the BBB acting as secondary carrier for drug-loaded AuNPs. characterized by NMR and techniques mentioned in the first part, as synthetized and in presence of PFOs and LPs.