Protein misfolding and amyloidosis in neurodegenerative diseases

The Platform on “protein misfolding and amyloidosis in neurodegenerative diseases” focuses mainly on the study of systemic amyloidosis, a group of diseases caused by the accumulation of proteins with altered structure into clusters called amyloid fibrosis.

In recent decades new categories of diseases have been described resulting from folding or abnormal folding of proteins. In particular, a common origin has been recognized related to the folding process for a group of diseases called amyloidoses. In the latters, the degenerate folding or misfolding is the basis of the formation of aggregates of fibrous nature which show the so-called cross-β structure, a generic way of folding of the polypeptide chain particularly stable, accessible in precise conditions both in vitro and in vivo, despite the diversity of sequence and corresponding native folding.

The work of INBB researchers has contributed significantly to the characterization of the intermediates of misfolding and aggregation mechanisms that lead to nucleation and to the identification of possible therapeutic strategies. The commitment of INBB researchers in the specific area is also reported from the activity reports submitted as part of the INBB National Conferences among which are mentioned the most recent ones related to INBB IX National Conference, held in Rome on 21-22 October 2010 and X INBB National Conference, held in Rome on 22-23 October 2012, whose detailed programs and abstracts of the reports are on this website www.inbb.it

The research future perspectives in the field of protein misfolding are linked to the progress in the ability of managing the events of pathological de-structuring with tools such as the use of osmolytes or molecular chaperones, able to modify the phase diagram of a protein in risk of fibril deposition, or the use of chaperone proteins, both exogenous and endogenous. Further perspectives of great interest are related to the applications of functionalized nano-particles, being studied in several INBB laboratories.

Several INBB RUs operate in the platform related to the “protein misfolding and amyloidosis in neurodegenerative diseases” firstly RUs of Florence, Genoa, Naples, Pavia and Udine.

SOME RECENT PUBLICATIONS

• Gümral D, Fogolari F, Corazza A, Viglino P, Giorgetti S, Stoppini M, Bellotti V, Esposito G. Reduction of conformational mobility and aggregation in W60G β2-microglobulin: assessment by 15N NMR relaxation. Magn Reson Chem. 2013 Dec;51(12):795-807. doi: 10.1002/mrc.4018. Epub 2013 Oct 18.
• Esposito G, Garvey M, Alverdi V, Pettirossi F, Corazza A, Fogolari F, Polano M, Mangione PP, Giorgetti S, Stoppini M, Rekas A, Bellotti V, Heck AJ, Carver JA. Monitoring the interaction between β2-microglobulin and the molecular chaperone αB-crystallin by NMR and mass spectrometry: αB-crystallin dissociates β2-microglobulin oligomers. J Biol Chem. 2013 Jun 14;288(24):17844-58.
• Fogolari F, Corazza A, Esposito G. A differential equation for the Generalized Born radii. Phys Chem Chem Phys. 2013 Jun 28;15(24):9783-91.
• Esposito G, Corazza A, Bellotti V. Pathological self-aggregation of β(2)-microglobulin: a challenge for protein biophysics. Subcell Biochem. 2012;65:165-83.
• Fogolari F, Corazza A, Viglino P, Esposito G. Fast structure similarity searches among protein models: efficient clustering of protein fragments. Algorithms Mol Biol. 2012 May 29;7(1):16.
• Fogolari F, Corazza A, Yarra V, Jalaru A, Viglino P, Esposito G. Bluues: a program for the analysis of the electrostatic properties of proteins based on generalized Born radii. BMC Bioinformatics. 2012 Mar 28;13 Suppl 4:S18.
• Rennella E, Corazza A, Codutti L, Causero A, Bellotti V, Stoppini M, Viglino P, Fogolari F, Esposito G. Single-shot NMR measurement of protein unfolding landscapes. Biochim Biophys Acta. 2012 Jun;1824(6):842-9.
• Fogolari F, Corazza A, Toppo S, Tosatto SC, Viglino P, Ursini F, Esposito G. Studying interactions by molecular dynamics simulations at high concentration. J Biomed Biotechnol. 2012;2012:303190.
• Rennella E, Corazza A, Codutti L, Bellotti V, Stoppini M, Viglino P, Fogolari F, Esposito G. Determining the energy landscape of proteins by a fast isotope exchange NMR approach. J Am Chem Soc. 2012 Mar 14;134(10):4457-60.
• Girometti R, Esposito G, Bagatto D, Avellini C, Bazzocchi M, Zuiani C. Is water diffusion isotropic in the cirrhotic liver? a study with diffusion-weighted imaging at 3.0 Tesla. Acad Radiol. 2012 Jan;19(1):55-61.