Amyloid diseases: from the molecular mechanism to the discovery of new drugs
Amyloid diseases: from the molecular mechanism to the discovery of new drugs
Research Group: Vittorio Bellotti, Patrizia Mangione, Sofia Giorgetti, Maurizia Valli, Sara Raimondi, Loredana Marchese, Guglielmo Verona
The research strategy of this group aims to elucidate the molecular events driving, in vivo, the conversion of soluble globular proteins into a insoluble polymeric fibrils.
We have a strong medical and biological background and a long tradition on studying amyloid diseases. See or web site for further details <http://www.amyloidresearch.it>. A PhD student will have the possibility to choose different specific projects:
1.Proper biochemical characterization of structural events occurring in vitro along the fibrillar transition
2. Characterize the biological events occurring in the C.elegans expressing amyloid proteins, both focusing of protein aggregation as well on the multisystem effects caused by such aggregates.
3. Discovery of new inhibitors of proteins amyloidogenesis. This last project is mostly based on a stable and strong collaboration with the National Amyloidosis Centre (NAC) of London UK where some of us (Bellotti and Mangione) have official positions. Students have the possibility to spend part of their research activity at NAC in UK. In particular through the NAC based activity we are running a program of drug discovery focused on the identification of small molecules suitable for the inhibition of the amyloid transition of human transthyretin and the characterization of novel mini-antibodies for the therapy of amyloidosis caused by human b2-microglobulin.
Recent Publications:
- Verona G, Mangione PP, Raimondi S, Giorgetti S, Faravelli G, Porcari R, Corazza A, Gillmore JD, Hawkins PN, Pepys MB, Taylor GW, Bellotti V. Inhibition of the mechano-enzymatic amyloidogenesis of transthyretin: role of ligand affinity, binding cooperativity and occupancy of the inner channel. Sci Rep. 2017 Mar 15;7(1):182.
- Valleix S, Verona G, Jourde-Chiche N, Nédelec B, Mangione PP, Bridoux F, Mangé A, Dogan A, Goujon JM, Lhomme M, Dauteuille C, Chabert M, Porcari R, Waudby CA, Relini A, Talmud PJ, Kovrov O, Olivecrona G, Stoppini M, Christodoulou J, Hawkins PN, Grateau G, Delpech M, Kontush A, Gillmore JD, Kalopissis AD, Bellotti V.
- D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile. Nat Commun. 2016 Jan 21;7:10353
Stoppini M, Bellotti V. Systemic amyloidosis: lessons from β2-microglobulin.J Biol Chem. 2015 Apr 17;290(16):9951-8