Amyloid Fibrils
Proteins are essential molecular machines that must fold into precise three-dimensional structures to function properly. However, under certain conditions, some proteins missfold and aggregate into amyloid fibrils—highly ordered, insoluble structures associated with neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and ALS. Understanding the formation and structural properties of amyloid fibrils is crucial for developing strategies to prevent or target these aggregates.
This research focuses on the structural characterization of amyloid fibrils, aiming to uncover the molecular mechanisms underlying their formation, stability, and interactions. By leveraging structural biology techniques, we seek to provide insights into the fundamental principles of amyloid aggregation, which could contribute to the development of novel therapeutic approaches.
This work is headed by Prof. Stefano Ricagno of the University of Milan.
Publications
Puri S, Gadda A, Polsinelli I, Barzago MM, Toto A, Sriramoju MK, Visentin C, Broggini L, Valérie Bonnet DM, Russo R, Chaves-Sanjuan A, Merlini G, Nuvolone M, Palladini G, Gianni S, Hsu SD, Diomede L, Ricagno S. The Critical Role of the Variable Domain in Driving Proteotoxicity and Aggregation in Full-length Light Chains. J Mol Biol. 2025 Mar 1;437(5):168958.
Schulte T, Chaves-Sanjuan A, Speranzini V, Sicking K, Milazzo M, Mazzini G, Rognoni P, Caminito S, Milani P, Marabelli C, Corbelli A, Diomede L, Fiordaliso F, Anastasia L, Pappone C, Merlini G, Bolognesi M, Nuvolone M, Fernández-Busnadiego R, Palladini G, Ricagno S. Helical superstructures between amyloid and collagen in cardiac fibrils from a patient with AL amyloidosis. Nat Commun. 2024 Jul 28;15(1):6359.
Puri S, Schulte T, Chaves-Sanjuan A, Mazzini G, Caminito S, Pappone C, Anastasia L, Milani P, Merlini G, Bolognesi M, Nuvolone M, Palladini G, Ricagno S. The Cryo-EM STRUCTURE of Renal Amyloid Fibril Suggests Structurally Homogeneous Multiorgan Aggregation in AL Amyloidosis. J Mol Biol. 2023 Sep 15;435(18):168215.
Garcia-Pardo J, Bartolomé-Nafría A, Chaves-Sanjuan A, Gil-Garcia M, Visentin C, Bolognesi M, Ricagno S, Ventura S. Cryo-EM structure of hnRNPDL-2 fibrils, a functional amyloid associated with limb-girdle muscular dystrophy D3. Nat Commun. 2023 Jan 16;14(1):239.
Schulte T, Chaves-Sanjuan A, Mazzini G, Speranzini V, Lavatelli F, Ferri F, Palizzotto C, Mazza M, Milani P, Nuvolone M, Vogt AC, Vogel M, Palladini G, Merlini G, Bolognesi M, Ferro S, Zini E, Ricagno S. Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter. Nat Commun. 2022 Nov 17;13(1):7041.