Proteins Aggregation

Aggregation processes can be certainly considered as one of the most interesting and challenging topics in current research. Such phenomenon is nowadays of critical interest in biophysics, biochemistry and protein-science since a large number of human diseases has been recognized to be associated with protein aggregation. As it is well known, deposits of aggregates, often ordered fibrils called amyloid, are associated with neurological pathologies like Alzheimer’s, Parkinson’s and Creutzfeldt-Jacob’s diseases. Moreover, oligomeric intermediates formed during aggregation kinetic are held to be key effectors of cytotoxicity and to cause a variety of amyloid related diseases.

Interestingly, even if amyloidogenic proteins or peptides do not share any sequence or structural homologies, the oligomers and fibrils are structurally similar. This suggests that common principles regulate both correct protein folding and aggregation . Protein aggregation is a complex phenomenon concerned with many-body transition between an initial (soluble precursors) and a final phase (insoluble aggregates) involving complex intra and intermolecular interactions modulated by initial protein structure and physico-chemical properties of the environment.

A general characteristic of such process appears to be a multiple interaction and cross-feedback among different mechanisms occurring on different length and time scales. This also results in the concurrent occurrence of different species, like partially folded monomers, oligomers and bigger aggregates during the aggregation pathway. Several mechanisms are involved in protein aggregation; among them: protein conformational changes (possibly including oligomer formation), nucleation and growth of different kinds of aggregates (amorphous structures, fibrils, fibers, gels) and phase transitions like the liquid-liquid demixing. The above mechanisms involve multiple interactions arising from both direct and solvent-induced forces which are equally effective at inter and intra-molecular level.

List of related papers

• Andersen CB, Hicks MR, Vetri V, Vandahl B, Rahbek-Nielsen H, Thøgersen H, Thøgersen IB, Enghild JJ, Serpell LC, Rischel C, Otzen DE, J.Mol Biol. (2010) 397 (2010) 932-946: "Glucagon fibril polymorphism reflects differences in protofilament backbone structure."
• V. Vetri, R. Carrotta, P. Picone, M. Di Carlo and V. Militello, Biochim. Biophys. Acta – Protein & Proteomics 1804, (2010) 173-183: "Concanavalin A aggregation and toxicity on cell cultures"
• Foderà V., Groenning M., Vetri V., Librizzi F., Spagnolo S., Cornett C., Olsen L., van de Weert M., Leone M. J. of Phys. Chem. B, (2008) 112 (47), 15174-15181: "Thioflavin T hydroxylation at basic pH and its effect on amyloid fibril detection "
• V. Vetri, F. Librizzi, M. Leone and V. Militello, European Biophysics Journal 36 (2007), 733-741: "Effect of Succinylation on thermal induced amyloid formation in Concanavalin A"
• V. Vetri, F. Librizzi, V. Militello and M. Leone , European Biophysics Journal 36 (2007), 717-725: "Thermal aggregation of bovine serum albumin at different pH: comparison with human serum albumin "
• Librizzi F., Foderà V., Vetri V., Lo Presti C. and Leone M. , European Biophysics Journal 36 (2007), 711-715: "Effects of confinement on insulin amyloid fibrils formation"
• V. Vetri, C. Canale, A. Relini, F. Librizzi, V. Militello, A. Gliozzi and M. Leone , ” Biophys Chem. 125 (2007), 184-190: "Amyloid fibrils formation and amorphous aggregation in concanavalin A"
• V. Vetri and V. Militello, ” Biophys Chem. 113 (2005), 89-91: "Thermal induced conformational changes involved in the aggregation pathways of beta-lactoglobulin"
• V. Militello, V. Vetri and M. Leone , ” Biophys Chem. 105 (2003), 133-141: "Conformational changes involved in thermal aggregation processes of Bovine Serum Albumin"