Protein aggregation and the onset of neurodegenerative diseases

Neurodegenerative diseases are among the most devastating diseases in terms of human suffering and economic cost. The understanding of the mechanism that leads to the formation of pathological aggregates (associated in many cases with brain damage), their structure (which depends on the path followed), their interaction with other molecules that can change (acceleration or slowing down) the brain damage, It is a major challenge for research in the biomedical / biotechnology sector. Convincing evidence indicates that the formation of pathological molecular aggregates from a monomeric solution is a complex process involving intermediates of various sizes and morphologies. In the case of Alzheimer's diseases, for example, during the nucleation phase, there are generally oligomers and small aggregates of different shapes and a large distribution of the dimensions, although there is no consensus that all of them take part in the formation of fibers. or some constitute the off-pathway aggregation product.
In recent years, soluble oligomers have attracted much attention, due to the strong correlation observed between their quantity and toxic effects. It is commonly accepted that the surface structure, shape and composition of oligomers probably represent important toxicity parameters. On the other hand, the amyloid polymorphism presents an experimental challenge also for the more sophisticated biophysical techniques due to the small size of the oligomers, the heterogeneous structures and the notorious structural sensitivity depending on the experimental conditions and the sample preparation methods. Our research has been aimed in the various years to understand the detailed structural characterization of oligomers with the aim of unveiling the mechanism that leads to the formation of pathological amyloid aggregates. Collaborations with biomedical researchers working in the field of neuroscience could cover the way for new therapeutic strategies based on molecular inhibitors

Members:
Donatella Bulone
Celeste Caruso Bavisotto
Maria Assunta Costa
Daniela Giacomazza
Valeria Guarrasi
Rosa Passantino
Pier Luigi San Biagio (Principal investigator)
Radha Santonocito