Palma Mangione

@unipv.it

Unit of Biochemistry, Department of Molecular Medicine, University of Pavia
University of Pavia, Italy

Palma Mangione


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Scopus Publications

Scopus Publications

  • Role of extracellular space and matrix remodeling in cardiac amyloidosis
    Francesca Lavatelli, Loredana Marchese, Palma Patrizia Mangione, Sara Raimondi, Diana Canetti, Guglielmo Verona, Lucia Venneri, Eloisa Arbustini, Laura Obici, Alessandra Corazza, Vittorio Bellotti, Sofia Giorgetti
    Matrix Biology, 2025
    The hallmark of amyloid diseases is deposition of misfolded proteins as amyloid fibrils in the interstitium of target organs. Amyloid deposits surround cells, distorting the micro and macro-architecture of the extracellular space and profoundly changing the physical and molecular properties of this compartment. In the heart, extracellular matrix (ECM) remodeling has a profound impact on the mechanical properties of this target organ and on the physiology and metabolism of resident cells. This review critically summarizes the available knowledge on ECM alterations in cardiac amyloidosis, with the goal of providing an overview on how biochemical, biophysical and anatomical modifications are interrelated, and how ECM remodeling participates in the pathophysiology of this unique type of cardiopathy.
  • Design and Mechanistic Analysis of a Potent Bivalent Inhibitor of Transthyretin Amyloid Fibrillogenesis
    P. Patrizia Mangione, Guglielmo Verona, Cristina Cantarutti, Paola Nocerino, Maria Chiara Mimmi, Christopher J. Swain, Diana Canetti, Sofia Giorgetti, Iain Uings, Julian D. Gillmore, Graham W. Taylor, Mark B. Pepys, Vittorio Bellotti, Alessandra Corazza
    Journal of Medicinal Chemistry, 2025
    Transthyretin amyloidosis (ATTR) is a systemic disease that primarily affects the heart and the peripheral nervous system. Despite available therapeutic options, advanced ATTR amyloidosis still presents unmet medical needs. We have therefore focused on the design of bivalent small molecules starting from our prototype palindromic ligand mds84, whose binding by transthyretin (TTR) greatly improves stability of the native structure by overcoming the negative cooperativity which is typical of monovalent stabilizers. Among the newly designed compounds here, we present B26, which is pseudoirreversibly bound by native TTR with faster entry kinetics into the protein molecule compared to mds84. It retains the ability to inhibit fibril formation in vitro, together with improved solubility. Using solution NMR, we show that B26 occupies both TTR binding sites simultaneously, leading to conformational effects distant from the binding site, including the proteolytic cleavage site involved in fibril formation by the mechano-enzymatic mechanism.
  • Truncation of the constant domain drives amyloid formation by immunoglobulin light chains
    Francesca Lavatelli, Antonino Natalello, Loredana Marchese, Diletta Ami, Alessandra Corazza, Sara Raimondi, Maria Chiara Mimmi, Silvia Malinverni, P. Patrizia Mangione, Manel Terrones Palmer, Alessio Lampis, Monica Concardi, Guglielmo Verona, Diana Canetti, Eloisa Arbustini, Vittorio Bellotti, Sofia Giorgetti
    Journal of Biological Chemistry, 2024
    AL amyloidosis is a life-threatening disease caused by deposition of immunoglobulin light chains. Whilst the mechanisms underlying light chains amyloidogenesis in vivo remain unclear, several studies have highlighted the role that tissue environment and structural amyloidogenicity of individual light chains have in the disease pathogenesis. AL natural deposits contain both full-length light chains and fragments encompassing the variable domain (V L ) as well as different length segments of the constant region (C L ), thus highlighting the relevance that proteolysis may have in the fibrillogenesis pathway. Here we investigate the role of major truncated species of the disease-associated AL55 light chain that were previously identified in natural deposits. Specifically, we study structure, molecular dynamics, thermal stability and capacity to form fibrils of a fragment containing both the V L and part of the C L (133-AL55), in comparison with the full-length protein and its variable domain alone, under shear stress and physiological conditions. Whereas the full-length light chain forms exclusively amorphous aggregates, both fragments generate fibrils, although, with different kinetics, aggregate structure and interplay with the unfragmented protein. More specifically, the V L -C L 133-AL55 fragment entirely converts into amyloid fibrils microscopically and spectroscopically similar to their ex vivo counterpart, and increases the amorphous aggregation of full-length AL55. Overall, our data support the idea that light chain structure and proteolysis are both relevant for amyloidogenesis in vivo, and provide a novel biocompatible model of light chain fibrillogenesis suitable for future mechanistic studies.
  • Degradation versus fibrillogenesis, two alternative pathways modulated by seeds and glycosaminoglycans
    Guglielmo Verona, Sara Raimondi, Diana Canetti, P. Patrizia Mangione, Loredana Marchese, Alessandra Corazza, Francesca Lavatelli, Julian D. Gillmore, Graham W. Taylor, Vittorio Bellotti, Sofia Giorgetti
    Protein Science, 2024
    The mechanism that converts native human transthyretin into amyloid fibrils in vivo is still a debated and controversial issue. Commonly, non‐physiological conditions of pH, temperature, or organic solvents are used in in vitro models of fibrillogenesis of globular proteins. Transthyretin amyloid formation can be achieved under physiological conditions through a mechano‐enzymatic mechanism involving specific serine proteases such as trypsin or plasmin. Here, we investigate S52P and L111M transthyretin variants, both causing a severe form of systemic amyloidosis mostly targeting the heart at a relatively young age with heterogeneous phenotype among patients. Our studies on thermodynamics show that both proteins are significantly less stable than other amyloidogenic variants. However, despite a similar thermodynamic stability, L111M variant seems to have enhanced susceptibility to cleavage and a lower tendency to form fibrils than S52P in the presence of specific proteases and biomechanical forces. Heparin strongly enhances the fibrillogenic capacity of L111M transthyretin, but has no effect on the S52P variant. Fibrillar seeds similarly affect the fibrillogenesis of both proteins, with a stronger effect on the L111M variant. According to our model of mechano‐enzymatic fibrillogenesis, both full‐length and truncated monomers, released after the first cleavage, can enter into fibrillogenesis or degradation pathways. Our findings show that the kinetics of the two processes can be affected by several factors, such as intrinsic amyloidogenicity due to the specific mutations, environmental factors including heparin and fibrillar seeds that significantly accelerate the fibrillogenic pathway.
  • Human wild-type and D76N β2-microglobulin variants are significant proteotoxic and metabolic stressors for transgenic C. elegans
    Sara Raimondi, Giulia Faravelli, Paola Nocerino, Valentina Mondani, Alma Baruffaldi, Loredana Marchese, Maria Chiara Mimmi, Diana Canetti, Guglielmo Verona, Marianna Caterino, Margherita Ruoppolo, P. Patrizia Mangione, Vittorio Bellotti, Francesca Lavatelli, Sofia Giorgetti
    FASEB Bioadvances, 2023
    β2‐microglobulin (β2‐m) is a plasma protein derived from physiological shedding of the class I major histocompatibility complex (MHCI), causing human systemic amyloidosis either due to persistently high concentrations of the wild‐type (WT) protein in hemodialyzed patients, or in presence of mutations, such as D76N β2‐m, which favor protein deposition in the adulthood, despite normal plasma levels. Here we describe a new transgenic Caenorhabditis elegans (C. elegans) strain expressing human WT β2‐m at high concentrations, mimicking the condition that underlies dialysis‐related amyloidosis (DRA) and we compare it to a previously established strain expressing the highly amyloidogenic D76N β2‐m at lower concentrations. Both strains exhibit behavioral defects, the severity of which correlates with β2‐m levels rather than with the presence of mutations, being more pronounced in WT β2‐m worms. β2‐m expression also has a deep impact on the nematodes' proteomic and metabolic profiles. Most significantly affected processes include protein degradation and stress response, amino acids metabolism, and bioenergetics. Molecular alterations are more pronounced in worms expressing WT β2‐m at high concentration compared to D76N β2‐m worms. Altogether, these data show that β2‐m is a proteotoxic protein in vivo also in its wild‐type form, and that concentration plays a key role in modulating pathogenicity. Our transgenic nematodes recapitulate the distinctive features subtending DRA compared to hereditary β2‐m amyloidosis (high levels of non‐mutated β2‐m vs. normal levels of variant β2‐m) and provide important clues on the molecular bases of these human diseases.
  • Calcium Binds to Transthyretin with Low Affinity
    Cristina Cantarutti, Maria Chiara Mimmi, Guglielmo Verona, Walter Mandaliti, Graham W. Taylor, P. Patrizia Mangione, Sofia Giorgetti, Vittorio Bellotti, Alessandra Corazza
    Biomolecules, 2022
    The plasma protein transthyretin (TTR), a transporter for thyroid hormones and retinol in plasma and cerebrospinal fluid, is responsible for the second most common type of systemic (ATTR) amyloidosis either in its wild type form or as a result of destabilizing genetic mutations that increase its aggregation propensity. The association between free calcium ions (Ca2+) and TTR is still debated, although recent work seems to suggest that calcium induces structural destabilization of TTR and promotes its aggregation at non-physiological low pH in vitro. We apply high-resolution NMR spectroscopy to investigate calcium binding to TTR showing the formation of labile interactions, which leave the native structure of TTR substantially unaltered. The effect of calcium binding on TTR-enhanced aggregation is also assessed at physiological pH through the mechano-enzymatic mechanism. Our results indicate that, even if the binding is weak, about 7% of TTR is likely to be Ca2+-bound in vivo and therefore more aggregation prone as we have shown that this interaction is able to increase the protein susceptibility to the proteolytic cleavage that leads to aggregation at physiological pH. These events, even if involving a minority of circulating TTR, may be relevant for ATTR, a pathology that takes several decades to develop.
  • Amyloid Formation by Globular Proteins: The Need to Narrow the Gap Between in Vitro and in Vivo Mechanisms
    Giulia Faravelli, Valentina Mondani, P. Patrizia Mangione, Sara Raimondi, Loredana Marchese, Francesca Lavatelli, Monica Stoppini, Alessandra Corazza, Diana Canetti, Guglielmo Verona, Laura Obici, Graham W. Taylor, Julian D. Gillmore, Sofia Giorgetti, Vittorio Bellotti
    Frontiers in Molecular Biosciences, 2022
    The globular to fibrillar transition of proteins represents a key pathogenic event in the development of amyloid diseases. Although systemic amyloidoses share the common characteristic of amyloid deposition in the extracellular matrix, they are clinically heterogeneous as the affected organs may vary. The observation that precursors of amyloid fibrils derived from circulating globular plasma proteins led to huge efforts in trying to elucidate the structural events determining the protein metamorphosis from their globular to fibrillar state. Whereas the process of metamorphosis has inspired poets and writers from Ovid to Kafka, protein metamorphism is a more recent concept. It is an ideal metaphor in biochemistry for studying the protein folding paradigm and investigating determinants of folding dynamics. Although we have learned how to transform both normal and pathogenic globular proteins into fibrillar polymers in vitro, the events occurring in vivo, are far more complex and yet to be explained. A major gap still exists between in vivo and in vitro models of fibrillogenesis as the biological complexity of the disease in living organisms cannot be reproduced at the same extent in the test tube. Reviewing the major scientific attempts to monitor the amyloidogenic metamorphosis of globular proteins in systems of increasing complexity, from cell culture to human tissues, may help to bridge the gap between the experimental models and the actual pathological events in patients.
  • Plasmin activity promotes amyloid deposition in a transgenic model of human transthyretin amyloidosis
    Ivana Slamova, Rozita Adib, Stephan Ellmerich, Michal R. Golos, Janet A. Gilbertson, Nicola Botcher, Diana Canetti, Graham W. Taylor, Nigel Rendell, Glenys A. Tennent, Guglielmo Verona, Riccardo Porcari, P. Patrizia Mangione, Julian D. Gillmore, Mark B. Pepys, Vittorio Bellotti, Philip N. Hawkins, Raya Al-Shawi, J. Paul Simons
    Nature Communications, 2021
    Cardiac ATTR amyloidosis, a serious but much under-diagnosed form of cardiomyopathy, is caused by deposition of amyloid fibrils derived from the plasma protein transthyretin (TTR), but its pathogenesis is poorly understood and informative in vivo models have proved elusive. Here we report the generation of a mouse model of cardiac ATTR amyloidosis with transgenic expression of human TTRS52P. The model is characterised by substantial ATTR amyloid deposits in the heart and tongue. The amyloid fibrils contain both full-length human TTR protomers and the residue 49-127 cleavage fragment which are present in ATTR amyloidosis patients. Urokinase-type plasminogen activator (uPA) and plasmin are abundant within the cardiac and lingual amyloid deposits, which contain marked serine protease activity; knockout of α2-antiplasmin, the physiological inhibitor of plasmin, enhances amyloid formation. Together, these findings indicate that cardiac ATTR amyloid deposition involves local uPA-mediated generation of plasmin and cleavage of TTR, consistent with the previously described mechano-enzymatic hypothesis for cardiac ATTR amyloid formation. This experimental model of ATTR cardiomyopathy has potential to allow further investigations of the factors that influence human ATTR amyloid deposition and the development of new treatments.
  • Clinical ApoA-IV amyloid is associated with fibrillogenic signal sequence
    Diana Canetti, Paola Nocerino, Nigel B Rendell, Nicola Botcher, Janet A Gilbertson, Angel Blanco, Dorota Rowczenio, Alessandra Morelli, P Patrizia Mangione, Alessandra Corazza, Guglielmo Verona, Sofia Giorgetti, Loredana Marchese, Per Westermark, Philip N Hawkins, Julian D Gillmore, Vittorio Bellotti, Graham W Taylor
    Journal of Pathology, 2021
    Apolipoprotein A‐IV amyloidosis is an uncommon form of the disease normally resulting in renal and cardiac dysfunction. ApoA‐IV amyloidosis was identified in 16 patients attending the National Amyloidosis Centre and in eight clinical samples received for histology review. Unexpectedly, proteomics identified the presence of ApoA‐IV signal sequence residues (p.18‐43 to p.20‐43) in 16/24 trypsin‐digested amyloid deposits but in only 1/266 non‐ApoA‐IV amyloid samples examined. These additional signal residues were also detected in the cardiac sample from the Swedish patient in which ApoA‐IV amyloid was first described, and in plasma from a single cardiac ApoA‐IV amyloidosis patient. The most common signal‐containing peptide observed in ApoA‐IV amyloid, p.20‐43, and to a far lesser extent the N‐terminal peptide, p.21‐43, were fibrillogenic in vitro at physiological pH, generating Congo red‐positive fibrils. The addition of a single signal‐derived alanine residue to the N‐terminus has resulted in markedly increased fibrillogenesis. If this effect translates to the mature circulating protein in vivo, then the presence of signal may result in preferential deposition as amyloid, perhaps acting as seed for the main circulating native form of the protein; it may also influence other ApoA‐IV‐associated pathologies. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
  • Comparative study of the stabilities of synthetic in vitro and natural ex vivo transthyretin amyloid fibrils
    Sara Raimondi, P. Patrizia Mangione, Guglielmo Verona, Diana Canetti, Paola Nocerino, Loredana Marchese, Rebecca Piccarducci, Valentina Mondani, Giulia Faravelli, Graham W. Taylor, Julian D. Gillmore, Alessandra Corazza, Mark B. Pepys, Sofia Giorgetti, Vittorio Bellotti
    Journal of Biological Chemistry, 2020
    Systemic amyloidosis caused by extracellular deposition of insoluble fibrils derived from the pathological aggregation of circulating proteins, such as transthyretin, is a severe and usually fatal condition. Elucidation of the molecular pathogenic mechanism of the disease and discovery of effective therapies still represents a challenging medical issue. The in vitro preparation of amyloid fibrils that exhibit structural and biochemical properties closely similar to those of natural fibrils is central to improving our understanding of the biophysical basis of amyloid formation in vivo and may offer an important tool for drug discovery. Here, we compared the morphology and thermodynamic stability of natural transthyretin fibrils with those of fibrils generated in vitro either using the common acidification procedure or primed by limited selective cleavage by plasmin. The free energies for fibril formation were −12.36, −8.10, and −10.61 kcal mol−1, respectively. The fibrils generated via plasmin cleavage were more stable than those prepared at low pH and were thermodynamically and morphologically similar to natural fibrils extracted from human amyloidotic tissue. Determination of thermodynamic stability is an important tool that is complementary to other methods of structural comparison between ex vivo fibrils and fibrils generated in vitro. Our finding that fibrils created via an in vitro amyloidogenic pathway are structurally similar to ex vivo human amyloid fibrils does not necessarily establish that the fibrillogenic pathway is the same for both, but it narrows the current knowledge gap between in vitro models and in vivo pathophysiology.
  • Lysozyme amyloid: evidence for the W64R variant by proteomics in the absence of the wild type protein
    Alexandra Moura, Paola Nocerino, Janet A. Gilbertson, Nigel B. Rendell, P. Patrizia Mangione, Guglielmo Verona, Dorota Rowczenio, Julian D. Gillmore, Graham W. Taylor, Vittorio Bellotti, Diana Canetti
    Amyloid, 2020
  • Diagnostic amyloid proteomics: Experience of the UK National Amyloidosis Centre
    Diana Canetti, Nigel B. Rendell, Janet A. Gilbertson, Nicola Botcher, Paola Nocerino, Angel Blanco, Lucia Di Vagno, Dorota Rowczenio, Guglielmo Verona, P. Patrizia Mangione, Vittorio Bellotti, Philip N. Hawkins, Julian D. Gillmore, Graham W. Taylor
    Clinical Chemistry and Laboratory Medicine, 2020
  • C. elegans expressing D76N β2-microglobulin: a model for in vivo screening of drug candidates targeting amyloidosis
    Giulia Faravelli, Sara Raimondi, Loredana Marchese, Frederick A. Partridge, Cristina Soria, P. Patrizia Mangione, Diana Canetti, Michele Perni, Francesco A. Aprile, Irene Zorzoli, Elia Di Schiavi, David A. Lomas, Vittorio Bellotti, David B. Sattelle, Sofia Giorgetti
    Scientific Reports, 2019
  • Binding of Monovalent and Bivalent Ligands by Transthyretin Causes Different Short- And Long-Distance Conformational Changes
    Alessandra Corazza, Guglielmo Verona, Christopher A. Waudby, P. Patrizia Mangione, Ryan Bingham, Iain Uings, Diana Canetti, Paola Nocerino, Graham W. Taylor, Mark B. Pepys, John Christodoulou, Vittorio Bellotti
    Journal of Medicinal Chemistry, 2019
  • Proteomic Analysis for the Diagnosis of Fibrinogen Aα-chain Amyloidosis
    Graham W. Taylor, Janet A. Gilbertson, Rabya Sayed, Angel Blanco, Nigel B. Rendell, Dorota Rowczenio, Tamer Rezk, P. Patrizia Mangione, Diana Canetti, Paul Bass, Philip N. Hawkins, Julian D. Gillmore
    Kidney International Reports, 2019
  • The complementary role of histology and proteomics for diagnosis and typing of systemic amyloidosis
    Tamer Rezk, Janet A Gilbertson, P Patrizia Mangione, Dorota Rowczenio, Nigel B Rendell, Diana Canetti, Helen J Lachmann, Ashutosh D Wechalekar, Paul Bass, Philip N Hawkins, Vittorio Bellotti, Graham W Taylor, Julian D Gillmore
    Journal of Pathology Clinical Research, 2019
  • Plasminogen activation triggers transthyretin amyloidogenesis in vitro
    P. Patrizia Mangione, Guglielmo Verona, Alessandra Corazza, Julien Marcoux, Diana Canetti, Sofia Giorgetti, Sara Raimondi, Monica Stoppini, Marilena Esposito, Annalisa Relini, Claudio Canale, Maurizia Valli, Loredana Marchese, Giulia Faravelli, Laura Obici, Philip N. Hawkins, Graham W. Taylor, Julian D. Gillmore, Mark B. Pepys, Vittorio Bellotti
    Journal of Biological Chemistry, 2018
  • Short-chain alkanethiol coating for small-size gold nanoparticles supporting protein stability
    Cristina Cantarutti, Paolo Bertoncin, Alessandra Corazza, Sofia Giorgetti, P. Mangione, Vittorio Bellotti, Federico Fogolari, Gennaro Esposito
    Magnetochemistry, 2017
  • Misidentification of transthyretin and immunoglobulin variants by proteomics due to methyl lysine formation in formalin-fixed paraffin-embedded amyloid tissue
    Diana Canetti, Nigel Brian Rendell, Lucia Di Vagno, Janet A. Gilbertson, Dorota Rowczenio, Tamar Rezk, Julian D. Gillmore, Phillip N. Hawkins, Guglielmo Verona, Palma Patrizia Mangione, Sofia Giorgetti, Pierluigi Mauri, Sara Motta, Antonella De Palma, Vittorio Bellotti, Graham W. Taylor
    Amyloid, 2017
  • Increasing the accuracy of proteomic typing by decellularisation of amyloid tissue biopsies
    P. Patrizia Mangione, Giuseppe Mazza, Janet A. Gilbertson, Nigel B. Rendell, Diana Canetti, Sofia Giorgetti, Luca Frenguelli, Marco Curti, Tamer Rezk, Sara Raimondi, Mark B. Pepys, Philip N. Hawkins, Julian D. Gillmore, Graham W. Taylor, Massimo Pinzani, Vittorio Bellotti
    Journal of Proteomics, 2017
  • Citrate-stabilized gold nanoparticles hinder fibrillogenesis of a pathological variant of β2-microglobulin
    Cristina Cantarutti, Sara Raimondi, Giorgia Brancolini, Alessandra Corazza, Sofia Giorgetti, Maurizio Ballico, Stefano Zanini, Giovanni Palmisano, Paolo Bertoncin, Loredana Marchese, P. Patrizia Mangione, Vittorio Bellotti, Stefano Corni, Federico Fogolari, Gennaro Esposito
    Nanoscale, 2017
  • Antiamyloidogenic and proamyloidogenic chaperone effects of C-reactive protein and serum amyloid P component
    Daisaku Ozawa, Ryo Nomura, P. Patrizia Mangione, Kazuhiro Hasegawa, Tadakazu Okoshi, Riccardo Porcari, Vittorio Bellotti, Hironobu Naiki
    Amyloid, 2017
  • Inhibition of the mechano-enzymatic amyloidogenesis of transthyretin: Role of ligand affinity, binding cooperativity and occupancy of the inner channel
    Guglielmo Verona, P. Patrizia Mangione, Sara Raimondi, Sofia Giorgetti, Giulia Faravelli, Riccardo Porcari, Alessandra Corazza, Julian D. Gillmore, Philip N. Hawkins, Mark B. Pepys, Graham W. Taylor, Vittorio Bellotti
    Scientific Reports, 2017
  • A specific nanobody prevents amyloidogenesis of D76N β2- microglobulin in vitro and modifies its tissue distribution in vivo
    Sara Raimondi, Riccardo Porcari, P. Patrizia Mangione, Guglielmo Verona, Julien Marcoux, Sofia Giorgetti, Graham W. Taylor, Stephan Ellmerich, Maurizio Ballico, Stefano Zanini, Els Pardon, Raya Al-Shawi, J. Paul Simons, Alessandra Corazza, Federico Fogolari, Manuela Leri, Massimo Stefani, Monica Bucciantini, Julian D. Gillmore, Philip N. Hawkins, Maurizia Valli, Monica Stoppini, Carol V. Robinson, Jan Steyaert, Gennaro Esposito, Vittorio Bellotti
    Scientific Reports, 2017
  • Multifaceted anti-amyloidogenic and pro-amyloidogenic effects of C-reactive protein and serum amyloid P component in vitro
    Daisaku Ozawa, Ryo Nomura, P. Patrizia Mangione, Kazuhiro Hasegawa, Tadakazu Okoshi, Riccardo Porcari, Vittorio Bellotti, Hironobu Naiki
    Scientific Reports, 2016
  • Co-fibrillogenesis of wild-type and D76N β2-microglobulin: The crucial role of fibrillar seeds
    Antonino Natalello, P. Patrizia Mangione, Sofia Giorgetti, Riccardo Porcari, Loredana Marchese, Irene Zorzoli, Annalisa Relini, Diletta Ami, Giulia Faravelli, Maurizia Valli, Monica Stoppini, Silvia M. Doglia, Vittorio Bellotti, Sara Raimondi
    Journal of Biological Chemistry, 2016
  • D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile
    Sophie Valleix, Guglielmo Verona, Noémie Jourde-Chiche, Brigitte Nédelec, P. Patrizia Mangione, Frank Bridoux, Alain Mangé, Ahmet Dogan, Jean-Michel Goujon, Marie Lhomme, Carolane Dauteuille, Michèle Chabert, Riccardo Porcari, Christopher A. Waudby, Annalisa Relini, Philippa J. Talmud, Oleg Kovrov, Gunilla Olivecrona, Monica Stoppini, John Christodoulou, Philip N. Hawkins, Gilles Grateau, Marc Delpech, Anatol Kontush, Julian D. Gillmore, Athina D. Kalopissis, Vittorio Bellotti
    Nature Communications, 2016
  • Amyloid persistence in decellularized liver: Biochemical and histopathological characterization
    Giuseppe Mazza, J. Paul Simons, Raya Al-Shawi, Stephan Ellmerich, Luca Urbani, Sofia Giorgetti, Graham W. Taylor, Janet A. Gilbertson, Andrew R. Hall, Walid Al-Akkad, Dipok Dhar, Philip N. Hawkins, Paolo De Coppi, Massimo Pinzani, Vittorio Bellotti, P. Patrizia Mangione
    Amyloid, 2016
  • Decoding the structural bases of D76N β2-microglobulin high amyloidogenicity through crystallography and asn-scan mutagenesis
    Matteo de Rosa, Alberto Barbiroli, Sofia Giorgetti, Patrizia P. Mangione, Martino Bolognesi, Stefano Ricagno
    Plos One, 2015
  • Enhanced toxicity of silver nanoparticles in transgenic Caenorhabditis elegans expressing amyloidogenic proteins
    Cristina Soria, Teresa Coccini, Uliana De Simone, Loredana Marchese, Irene Zorzoli, Sofia Giorgetti, Sara Raimondi, P. Patrizia Mangione, Stefano Ramat, Vittorio Bellotti, Luigi Manzo, Monica Stoppini
    Amyloid, 2015
  • Capillary electrophoresis analysis of different variants of the amyloidogenic protein β2-microglobulin as a simple tool for misfolding and stability studies
    Laura Bertoletti, Federica Bisceglia, Raffaella Colombo, Sofia Giorgetti, Sara Raimondi, P. Patrizia Mangione, Ersilia De Lorenzi
    Electrophoresis, 2015
  • A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis
    Julien Marcoux, P Patrizia Mangione, Riccardo Porcari, Matteo T Degiacomi, Guglielmo Verona, Graham W Taylor, Sofia Giorgetti, Sara Raimondi, Sarah Sanglier‐Cianférani, Justin LP Benesch, Ciro Cecconi, Mohsin M Naqvi, Julian D Gillmore, Philip N Hawkins, Monica Stoppini, Carol V Robinson, Mark B Pepys, Vittorio Bellotti
    EMBO Molecular Medicine, 2015
  • Bifunctional crosslinking ligands for transthyretin
    P. Patrizia Mangione, Stéphanie Deroo, Stephan Ellmerich, Vittorio Bellotti, Simon Kolstoe, Stephen P. Wood, Carol V. Robinson, Martin D. Smith, Glenys A. Tennent, Robert J. Broadbridge, Claire E. Council, Joanne R. Thurston, Victoria A. Steadman, Antonio K. Vong, Christopher J. Swain, Mark B. Pepys, Graham W. Taylor
    Open Biology, 2015
  • The H50Q mutation induces a 10-fold decrease in the solubility of α-synuclein
    Riccardo Porcari, Christos Proukakis, Christopher A. Waudby, Benedetta Bolognesi, P. Patrizia Mangione, Jack F.S. Paton, Stephen Mullin, Lisa D. Cabrita, Amanda Penco, Annalisa Relini, Guglielmo Verona, Michele Vendruscolo, Monica Stoppini, Gian Gaetano Tartaglia, Carlo Camilloni, John Christodoulou, Anthony H.V. Schapira, Vittorio Bellotti
    Journal of Biological Chemistry, 2015
  • Class I major histocompatibility complex, the Trojan Horse for secretion of Amyloidogenic β2-Microglobulin
    Levon Halabelian, Stefano Ricagno, Sofia Giorgetti, Carlo Santambrogio, Alberto Barbiroli, Sara Pellegrino, Adnane Achour, Rita Grandori, Loredana Marchese, Sara Raimondi, P. Patrizia Mangione, Gennaro Esposito, Raya Al-Shawi, J. Paul Simons, Ivana Speck, Monica Stoppini, Martino Bolognesi, Vittorio Bellotti
    Journal of Biological Chemistry, 2014
  • Proteolytic cleavage of Ser52Pro variant transthyretin triggers its amyloid fibrillogenesis
    P. Patrizia Mangione, Riccardo Porcari, Julian D. Gillmore, Piero Pucci, Maria Monti, Mattia Porcari, Sofia Giorgetti, Loredana Marchese, Sara Raimondi, Louise C. Serpell, Wenjie Chen, Annalisa Relini, Julien Marcoux, Innes R. Clatworthy, Graham W. Taylor, Glenys A. Tennent, Carol V. Robinson, Philip N. Hawkins, Monica Stoppini, Stephen P. Wood, Mark B. Pepys, Vittorio Bellotti
    Proceedings of the National Academy of Sciences of the United States of America, 2014
  • Structure, folding dynamics, and amyloidogenesis of D76N β2-microglobulin roles of shear flow, hydrophobic surfaces, and α-crystallin
    P. Patrizia Mangione, Gennaro Esposito, Annalisa Relini, Sara Raimondi, Riccardo Porcari, Sofia Giorgetti, Alessandra Corazza, Federico Fogolari, Amanda Penco, Yuji Goto, Young-Ho Lee, Hisashi Yagi, Ciro Cecconi, Mohsin M. Naqvi, Julian D. Gillmore, Philip N. Hawkins, Fabrizio Chiti, Ranieri Rolandi, Graham W. Taylor, Mark B. Pepys, Monica Stoppini, Vittorio Bellotti
    Journal of Biological Chemistry, 2013
  • Pathogenetic mechanisms of amyloid A amyloidosis
    J. Paul Simons, Raya Al-Shawi, Stephan Ellmerich, Ivana Speck, Samrina Aslam, Winston L. Hutchinson, Palma P. Mangione, Petra Disterer, Janet A. Gilbertson, Toby Hunt, David J. Millar, Shane Minogue, Karl Bodin, Mark B. Pepys, Philip N. Hawkins
    Proceedings of the National Academy of Sciences of the United States of America, 2013
  • Benefit of doxycycline treatment on articular disability caused by dialysis related amyloidosis
    Giovanni Montagna, Benedetta Cazzulani, Laura Obici, Carla Uggetti, Sofia Giorgetti, Riccardo Porcari, Rubina Ruggiero, P. Patrizia Mangione, Moreno Brambilla, Jacopo Lucchetti, Giovanna Guiso, Marco Gobbi, Giampaolo Merlini, Mario Salmona, Monica Stoppini, Giuseppe Villa, Vittorio Bellotti
    Amyloid, 2013
  • Monitoring the interaction between β2-microglobulin and the molecular chaperone αB-crystallin by NMR and mass spectrometry: αB-crystallin dissociates β2-microglobulin oligomers
    Gennaro Esposito, Megan Garvey, Vera Alverdi, Fabio Pettirossi, Alessandra Corazza, Federico Fogolari, Maurizio Polano, P. Patrizia Mangione, Sofia Giorgetti, Monica Stoppini, Agata Rekas, Vittorio Bellotti, Albert J.R. Heck, John A. Carver
    Journal of Biological Chemistry, 2013
  • Distribution and determinants of circulating complement factor H concentration determined by a high-throughput immunonephelometric assay
    Reecha Sofat, P. Patrizia Mangione, J. Ruth Gallimore, Svetlana Hakobyan, Timothy R. Hughes, Tina Shah, Tim Goodship, Francesco D'Aiuto, Claudia Langenberg, Nick Wareham, B. Paul Morgan, Mark B. Pepys, Aroon D. Hingorani
    Journal of Immunological Methods, 2013
  • C. elegans Expressing Human β2-Microglobulin: A Novel Model for Studying the Relationship between the Molecular Assembly and the Toxic Phenotype
    Luisa Diomede, Cristina Soria, Margherita Romeo, Sofia Giorgetti, Loredana Marchese, Patrizia Palma Mangione, Riccardo Porcari, Irene Zorzoli, Mario Salmona, Vittorio Bellotti, Monica Stoppini
    Plos One, 2012
  • Isolation and characterization of pharmaceutical grade human pentraxins, serum amyloid P component and C-reactive protein, for clinical use
    Mark B. Pepys, J. Ruth Gallimore, Joanne Lloyd, Zhanhong Li, David Graham, Graham W. Taylor, Stephan Ellmerich, Palma P. Mangione, Glenys A. Tennent, Winston L. Hutchinson, David J. Millar, Gary Bennett, John More, David Evans, Yogesh Mistry, Stephen Poole, Philip N. Hawkins
    Journal of Immunological Methods, 2012
  • Hereditary systemic amyloidosis due to Asp76Asn variant β2-microglobulin
    Sophie Valleix, Julian D. Gillmore, Frank Bridoux, Palma P. Mangione, Ahmet Dogan, Brigitte Nedelec, Mathieu Boimard, Guy Touchard, Jean-Michel Goujon, Corinne Lacombe, Pierre Lozeron, David Adams, Catherine Lacroix, Thierry Maisonobe, Violaine Planté-Bordeneuve, Julie A. Vrana, Jason D. Theis, Sofia Giorgetti, Riccardo Porcari, Stefano Ricagno, Martino Bolognesi, Monica Stoppini, Marc Delpech, Mark B. Pepys, Philip N. Hawkins, Vittorio Bellotti
    New England Journal of Medicine, 2012
  • Effects of the known pathogenic mutations on the aggregation pathway of the amyloidogenic peptide of apolipoprotein A-I
    Sara Raimondi, Fulvio Guglielmi, Sofia Giorgetti, Sonia Di Gaetano, Angela Arciello, Daria M. Monti, Annalisa Relini, Daniela Nichino, Silvia M. Doglia, Antonino Natalello, Piero Pucci, Palma Mangione, Laura Obici, Giampaolo Merlini, Monica Stoppini, Paul Robustelli, Gian Gaetano Tartaglia, Michele Vendruscolo, Christopher M. Dobson, Renata Piccoli, Vittorio Bellotti
    Journal of Molecular Biology, 2011
  • Effect of tetracyclines on the dynamics of formation and destructuration of β2-microglobulin amyloid fibrils
    Sofia Giorgetti, Sara Raimondi, Katiuscia Pagano, Annalisa Relini, Monica Bucciantini, Alessandra Corazza, Federico Fogolari, Luca Codutti, Mario Salmona, Palma Mangione, Lino Colombo, Ada De Luigi, Riccardo Porcari, Alessandra Gliozzi, Massimo Stefani, Gennaro Esposito, Vittorio Bellotti, Monica Stoppini
    Journal of Biological Chemistry, 2011
  • Structural basis of ligand specificity in the human pentraxins, C-reactive protein and serum amyloid P component
    Halina Mikolajek, Simon E. Kolstoe, Valerie E. Pye, Palma Mangione, Mark B. Pepys, Stephen P. Wood
    Journal of Molecular Recognition, 2011
  • The intracellular quality control system down-regulates the secretion of amyloidogenic apolipoprotein A-I variants: A possible impact on the natural history of the disease
    Marta Marchesi, Cinzia Parolini, Caterina Valetti, Palma Mangione, Laura Obici, Sofia Giorgetti, Sara Raimondi, Simona Donadei, Gina Gregorini, Giampaolo Merlini, Monica Stoppini, Giulia Chiesa, Vittorio Bellotti
    Biochimica Et Biophysica Acta Molecular Basis of Disease, 2011
  • The two tryptophans of 2-microglobulin have distinct roles in function and folding and might represent two independent responses to evolutionary pressure
    Sara Raimondi, Nicola Barbarini, Palma Mangione, Gennaro Esposito, Stefano Ricagno, Martino Bolognesi, Irene Zorzoli, Loredana Marchese, Cristina Soria, Riccardo Bellazzi, Maria Monti, Monica Stoppini, Mario Stefanelli, Paolo Magni, Vittorio Bellotti
    BMC Evolutionary Biology, 2011
  • Trapping of palindromic ligands within native transthyretin prevents amyloid formation
    Simon E. Kolstoe, Palma P. Mangione, Vittorio Bellotti, Graham W. Taylor, Glenys A. Tennent, Stéphanie Deroo, Angus J. Morrison, Alexander J. A. Cobb, Anthony Coyne, Margaret G. McCammon, Timothy D. Warner, Jane Mitchell, Raj Gill, Martin D. Smith, Steven V. Ley, Carol V. Robinson, Stephen P. Wood, Mark B. Pepys
    Proceedings of the National Academy of Sciences of the United States of America, 2010
  • Antibodies to human serum amyloid P component eliminate visceral amyloid deposits
    Karl Bodin, Stephan Ellmerich, Melvyn C. Kahan, Glenys A. Tennent, Andrzej Loesch, Janet A. Gilbertson, Winston L. Hutchinson, Palma P. Mangione, J. Ruth Gallimore, David J. Millar, Shane Minogue, Amar P. Dhillon, Graham W. Taylor, Arthur R. Bradwell, Aviva Petrie, Julian D. Gillmore, Vittorio Bellotti, Marina Botto, Philip N. Hawkins, Mark B. Pepys
    Nature, 2010
  • Complement factor H binds to denatured rather than to native pentameric C-reactive protein
    Svetlana Hakobyan, Claire L. Harris, Carmen W. van den Berg, Maria Carmen Fernandez-Alonso, Elena Goicoechea de Jorge, Santiago Rodriguez de Cordoba, German Rivas, Palma Mangione, Mark B. Pepys, B. Paul Morgan
    Journal of Biological Chemistry, 2008
  • Sulfonated molecules that bind a partially structured species of β2-microglobulin also influence refolding and fibrillogenesis
    Chiara Carazzone, Raffaella Colombo, Milena Quaglia, Palma Mangione, Sara Raimondi, Sofia Giorgetti, Gabriele Caccialanza, Vittorio Bellotti, Ersilia De Lorenzi
    Electrophoresis, 2008
  • Recombinant amyloidogenic domain of ApoA-I: Analysis of its fibrillogenic potential
    Sonia Di Gaetano, Fulvio Guglielmi, Angela Arciello, Palma Mangione, Maria Monti, Daniela Pagnozzi, Sara Raimondi, Sofia Giorgetti, Stefania Orrù, Claudio Canale, Piero Pucci, Christopher M. Dobson, Vittorio Bellotti, Renata Piccoli
    Biochemical and Biophysical Research Communications, 2006
  • Micro-heterogeneity and aggregation in β2-microglobulin solutions: Effects of temperature, pH, and conformational variant addition
    Roberto Piazza, Matteo Pierno, Sara Iacopini, Palma Mangione, Gennaro Esposito, Vittorio Bellotti
    European Biophysics Journal, 2006
  • Solution structure of β2-microglobulin and insights into fibrillogenesis
    Gennaro Esposito, Alessandra Corazza, Paolo Viglino, Giuliana Verdone, Fabio Pettirossi, Federico Fogolari, Ads Makek, Sofia Giorgetti, Palma Mangione, Monica Stoppini, Vittorio Bellotti
    Biochimica Et Biophysica Acta Proteins and Proteomics, 2005
  • Proteomics of β2-microglobulin amyloid fibrils
    Monica Stoppini, Palma Mangione, Maria Monti, Sofia Giorgetti, Loredana Marchese, Patrizia Arcidiaco, Laura Verga, Siro Segagni, Piero Pucci, Giampaolo Merlini, Vittorio Bellotti
    Biochimica Et Biophysica Acta Proteins and Proteomics, 2005
  • β2-Microglobulin isoforms display an heterogeneous affinity for type I collagen
    Sofia Giorgetti, Antonio Rossi, Palma Mangione, Sara Raimondi, Sara Marini, Monica Stoppini, Alessandra Corazza, Paolo Viglino, Gennaro Esposito, Giuseppe Cetta, Giampaolo Merlini, Vittorio Bellotti
    Protein Science, 2005
  • Properties of Some Variants of Human β2- Microglobulin and Amyloidogenesis
    Alessandra Corazza, Fabio Pettirossi, Paolo Viglino, Giuliana Verdone, Julian Garcia, Pascal Dumy, Sofia Giorgetti, Palma Mangione, Sara Raimondi, Monica Stoppini, Vittorio Bellotti, Gennaro Esposito
    Journal of Biological Chemistry, 2004
  • β2-Microglobulin H31Y Variant 3D Structure Highlights the Protein Natural Propensity Towards Intermolecular Aggregation
    C Rosano, S Zuccotti, P Mangione, S Giorgetti, V Bellotti, F Pettirossi, A Corazza, P Viglino, G Esposito, M Bolognesi
    Journal of Molecular Biology, 2004
  • Structural and folding dynamic properties of the T70N variant of human lysozyme
    Gennaro Esposito, Julian Garcia, Palma Mangione, Sofia Giorgetti, Alessandra Corazza, Paolo Viglino, Fabrizio Chiti, Alessia Andreola, Pascal Dumy, David Booth, Philip N. Hawkins, Vittorio Bellotti
    Journal of Biological Chemistry, 2003
  • Preliminary crystallographic characterization of the human β2 microglobulin His31Tyr mutant in a tetrameric assembly
    Simone Zuccotti, Camillo Rosano, Palma Mangione, Vittorio Bellotti, Martino Bolognesi
    Acta Crystallographica Section D Biological Crystallography, 2003
  • Conformational switching and fibrillogenesis in the amyloidogenic fragment of apolipoprotein A-I
    Alessia Andreola, Vittorio Bellotti, Sofia Giorgetti, Palma Mangione, Laura Obici, Monica Stoppini, Jaume Torres, Enrico Monzani, Giampaolo Merlini, Margaret Sunde
    Journal of Biological Chemistry, 2003
  • Topological investigation of amyloid fibrils obtained from β2-microglobulin
    Maria Monti, Serena Principe, Sofia Giorgetti, Palma Mangione, Gianpaolo Merlini, Anne Clark, Vittorio Bellotti, Angela Amoresano, Piero Pucci
    Protein Science, 2002
  • The solution structure of human β2-microglobulin reveals the prodromes of its amyloid transition
    Giuliana Verdone, Alessandra Corazza, Paolo Viglino, Fabio Pettirossi, Sofia Giorgetti, Palma Mangione, Alessia Andreola, Monica Stoppini, Vittorio Bellotti, Gennaro Esposito
    Protein Science, 2002
  • Capillary electrophoresis investigation of a partially unfolded conformation of β2-microglobulin
    Ersilia De Lorenzi, Silvia Grossi, Gabriella Massolini, Sofia Giorgetti, Palma Mangione, Alessia Andreola, Fabrizio Chiti, Vittorio Bellotti, Gabriele Caccialanza
    Electrophoresis, 2002
  • A Partially Structured Species of β2-Microglobulin Is Significantly Populated under Physiological Conditions and Involved in Fibrillogenesis
    Fabrizio Chiti, Ersilia De Lorenzi, Silvia Grossi, Palma Mangione, Sofia Giorgetti, Gabriele Caccialanza, Christopher M. Dobson, Giampaolo Merlini, Giampietro Ramponi, Vittorio Bellotti
    Journal of Biological Chemistry, 2001
  • Amyloid fibrils derived from the apolipoprotein A1 Leu174Ser variant contain elements of ordered helical structure
    Palma Mangione, Margaret Sunde, Sofia Giorgetti, Monica Stoppini, Gennaro Esposito, Luca Gianelli, Laura Obici, Lia Asti, Alessia Andreola, Paolo Viglino, Giampaolo Merlini, Vittorio Bellotti
    Protein Science, 2001
  • Detection of two partially structured species in the folding process of the amyloidogenic protein β2-microglobulin
    Fabrizio Chiti, Palma Mangione, Alessia Andreola, Sofia Giorgetti, Massimo Stefani, Christopher M. Dobson, Vittorio Bellotti, Niccolò Taddei
    Journal of Molecular Biology, 2001
  • Hepatitis C virus-associated cryoglobulinaemic glomerulonephritis with delayed appearance of monoclonal cryoglobulinaemia [4]
    Giovanni Montagna, Valter Piazza, Giovanni Banfi, Vittorio Bellotti, Siro Segagni, Loredana Picardi, Palma Mangione, Sofia Giorgetti, Irene Zorzoli, Antonella Cerino, Alessandro Salvadeo
    Nephrology Dialysis Transplantation, 2001
  • Review: Immunoglobulin light chain amyloidosis - The archetype of structural and pathogenic variability
    Vittorio Bellotti, Palma Mangione, Giampaolo Merlini
    Journal of Structural Biology, 2000
  • Detection of fragments of β2-microglobulin in amyloid fibrils [5]
    Monica Stoppini, Patrizia Arcidiaco, Palma Mangione, Sofia Giorgetti, Diego Brancaccio, Vittorio Bellotti
    Kidney International, 2000
  • Affinity capillary electrophoresis is a powerful tool to identify transthyretin binding drugs for potential therapeutic use in amyloidosis
    Ersilia De Lorenzi, Chiara Galbusera, Vittorio Bellotti, Palma Mangione, Gabriella Massolini, Elena Tabolotti, Alessia Andreola, Gabriele Caccialanza
    Electrophoresis, 2000
  • Conformational dynamics of the β2-microglobulin C terminal in the cell-membrane-anchored major histocompatibility complex type I
    M. Massa, P. Mangione, P. Pignatti, M. Stoppini, G. Zanotti, P. Arcidiaco, G. Merlini, G. Ferri, V. Bellotti*
    Cellular and Molecular Life Sciences, 2000
  • Removal of the N-terminal hexapeptide from human β2-microglobulin facilities protein aggregation and fibril formation
    G. Esposito, R. Michelutti, G. Verdone, P. Viglino, H. Hern ÁNdez, C. V. Robinson, A. Amoresano, F. Dal Piaz, M. Monti, P. Pucci, P. Mangione, M. Stoppini, G. Merlini, G. Ferri, V. Bellotti
    Protein Science, 2000
  • Effects of a vitamin E-modified dialyzer (excebrane®) on beta-2-microglobulin structure and removal
    Contributions to Nephrology, 1999
  • Biological activity and pathological implications of misfolded proteins
    V. Bellotti, P. Mangione, M. Stoppini
    Cellular and Molecular Life Sciences, 1999
  • The new apolipoprotein A-I variant Leu174 → Ser causes hereditary cardiac amyloidosis, and the amyloid fibrils are constituted by the 93- residue N-terminal polypeptide
    Laura Obici, Vittorio Bellotti, Palma Mangione, Monica Stoppini, Eloisa Arbustini, Laura Verga, Irene Zorzoli, Ernesto Anesi, Giuseppe Zanotti, Carlo Campana, Mario Viganò, Giampaolo Merlini
    American Journal of Pathology, 1999
  • β2-Microglobulin can be refolded into a native state from ex vivo amyloid fibrils
    Vittorio Bellotti, Monica Stoppini, Palma Mangione, Margaret Sunde, Carol Robinson, Lia Asti, Diego Brancaccio, Giuseppina Ferri
    European Journal of Biochemistry, 1998
  • Evidence that amyloidogenic light chains undergo antigen-driven selection
    Vittorio Perfetti, Paola Ubbiali, Maurizio Colli Vignarelli, Marta Diegoli, Roberta Fasani, Monica Stoppini, Antonella Lisa, Palma Mangione, Laura Obici, Eloisa Arbustini, Giampaolo Merlini
    Blood, 1998
  • Use of anti-(β2 microglobulin) mAb to study formation of amyloid fibrils
    Monica Stoppini, Vittorio Bellotti, Palma Mangione, Giampaolo Merlini, Giuseppina Ferri
    European Journal of Biochemistry, 1997
  • Structural and functional characterization of three human immunoglobulin κ light chains with different pathological implications
    Vittorio Bellotti, Monica Stoppini, Palma P. Mangione, Alessandro Fornasieri, Li Min, Giampaolo Merlini, Giuseppina Ferri
    Biochimica Et Biophysica Acta Molecular Basis of Disease, 1996