Protein biochemistry and protein misfolding diseases - Vittorio Bellotti

Systemic amyloidoses are a group of severe diseases, in which human proteins lose their native globular structure and aggregate as extracellular amyloid fibrils, thus damaging the architecture and function of affected organs. Many forms of systemic amyloidoses are aging-related, and this problem is progressively growing in parallel to the increased life expectancy of our society. The mechanisms that govern the onset, anatomical distribution and progression of amyloid deposition are still poorly understood.

 

Our research aims to elucidate the mechanism of conversion of amyloidogenic globular proteins to fibrils, in the perspective of understanding the events occurring in the physiological environment in the major forms of systemic amyloidosis. To this aim, we exploit biocompatible in vitro and in vivo experimental systems, and we explore the biological factors that modulate the natural history of the disease, mainly the interaction with components of the microenvironment, biomechanical forces, post-translational modifications.

 

The current research activity of the laboratory is focused on:

- Transthyretin (TTR), causing hereditary (ATTRh) or aging-related (ATTRwt) ATTR amyloidosis;

- β2-microglobulin (β2-m), causing hereditary or dialysis-associated amyloidosis;

- Immunoglobulin light chains, causing light chain amyloidosis (AL amyloidosis).

 

Our research is based on advanced technologies, including NMR, spectroscopic and proteomics approaches. Specifically developed experimental systems include decellularized tissues and animal models, in particular transgenic C. elegans strains expressing β2-m isoforms, and a murine model for a pathogenic TTR variant. Through these systems we can test, at a preclinical level, potential therapeutic strategies under developme