Amyloid aggregation processes and their inhibition
The study of the mechanisms underlying protein amyloid formation and deposition is nowadays one of the most challenging research topics in biophysics. The primary interest comes from the involvement of amyloid formation in the etiology of a number of disorders, including Parkinson’s and Alzheimer’s disease, all characterized by the abnormal deposition within tissues of amyloid aggregates. The understanding at a molecular level of the mechanisms leading to the formation of amyloid species is fundamental to design effective inhibition strategies, with clear implications in medical, pharmaceutical and biotechnological research. In this framework, our activity is devoted at proteins directly involved in pathologies, as the Abeta peptide in Alzheimer’s disease, but it makes also use of suitable model systems, such as Insulin or Concanavalin, characterized by analogous amyloid aggregation pathways.
Beyond the biophysical understanding of the basic mechanisms leading to amyloid formation, considerable interest is devoted to its inhibition considering both natural, as alfaS1-caseina, and synthetic molecules, as oxadiazole derivatives. The interesting inhibitory action of the molecular chaperone Heat Shock Proteins 60 (Hsp60), on Abeta peptide aggregation, has launched a new project aimed to the Characterization of the Heat Shock Factor 1 (HSF1) and its molecular complexes. In fact, the modulation of the expression of Heat Shock Proteins through HSF1 is a potential therapeutic target for the treatment of protein misfolding diseases). Finally, suitable Membrane model systems (unilamellar vesicles or in general lipid bilayer) are used for the evaluation of the toxicity of the various protein aggregates and for the evaluation of protective effects obtained by fibril inhibiting molecules.
Members:
Rita Carrotta (Principal investigator)
Fabio Librizzi
Maria Rosalia Mangione (Principal investigator)
Vincenzo Martorana
Silvia Vilasi