Margherita Romeo

Verified @gmail.com

Department of Biochemistry and Molecular Pharmacology
Istiituto di Ricerche Farmacologiche Mario Negri IRCCS

Margherita Romeo


         Download Compact PDF  
https://researchid.co/margherita

RESEARCH, TEACHING, or OTHER INTERESTS

General Biochemistry, Genetics and Molecular Biology
31

Scopus Publications

Scopus Publications

  • A Lecithin-Based Delivery Form of Quercetin Promotes Stress Resistance and Longevity in Caenorhabditis elegans
    Margherita Romeo, Maria Monica Barzago, Claudia Fracasso, Manuel Nettis, Antonella Riva, Marco Gobbi, Serena Tongiani, Luisa Diomede
    Pharmaceuticals, 2026
    Background/Objectives: The flavonoid quercetin (Q) has recently been suggested as a natural anti-aging and senolytic agent. However, its low stability and poor oral bioavailability may limit its efficacy. To address this, we investigated whether a lecithin-based formulation of Q, Quercefit™ (QF), enhances stress resistance and delays aging in vivo. Methods: The nematode Caenorhabditis elegans was used as an animal model to evaluate the effects of QF under physiological and stress conditions. Unformulated Q was administered as a control. Worm survival, healthspan, resistance to thermal and oxidative stress, and expression of stress- and longevity-related genes were assessed. All the experiments were conducted at least in triplicate, each including a minimum of 15 worms. The data were analyzed using Student’s t-test, one-way or two-way ANOVA, and Bonferroni’s post hoc test. Results: One hundred micromolar Q administered in QF was more effective than equimolar unformulated Q in increasing the worms’ ability to resist acute thermal stress at 35 °C (tested on 75 worms/group) and oxidative stress caused by 0.5 mM hydrogen peroxide (tested on 75 worms/group). In this last case, the protective effect of QF was similar to that of N-acetylcysteine and ascorbic acid. Under experimental conditions mimicking the long-term consequences of thermal stress, QF, like Q, increased the worms’ lifespan and healthspan by approximately 50%, counteracting the age-related decline associated with stress (120 worms/group). These benefits are supported by QF’s capacity to act as a reactive oxygen species scavenger; suppress heat-shock element gene transcription activated by thermal stress, such as hsp-16.2 and hsp-70, and stimulate the sod-3 and gst-4 genes that are involved in antioxidant and detoxification responses. Conclusions: These findings suggest that Q, when administered in the QF formulation, can act at the transcriptional level to protect against aging induced by stressful conditions.
  • Increased ectodysplasin-A2-receptor EDA2R is a ubiquitous hallmark of aging and mediates parainflammatory responses
    Maria Chiara Barbera, Luca Guarrera, Andrea David Re Cecconi, Giada Andrea Cassanmagnago, Arianna Vallerga, Martina Lunardi, Francesca Checchi, Laura Di Rito, Margherita Romeo, Sarah Natalia Mapelli, Benedikt Schoser, Edward V. Generozov, , Rinat I. Sultanov, Alexandra Kanygina, Nikolay A. Kulemin, Ekaterina A. Semenova, Rick Jansen, Eco J. C. de Geus, Brenda Penninx, Jenny van Dongen, Ilaria Craparotta, Rosanna Piccirillo, Ildus I. Ahmetov, Marco Bolis
    Nature Communications, 2025
    Intensive efforts have been made to identify features that could serve as biomarkers of aging. Yet, drug-based interventions aimed at lessening the detrimental effects of getting older are lacking. This is largely attributable to tissue-specificity, sex-related differences, and to the difficulty of identifying actionable targets, which continues to pose a significant challenge. Here, we implement a bioinformatics approach revealing that aging-associated increase of the transmembrane Ectodysplasin-A2-Receptor is a prominent tissue-independent alteration occurring in humans and other species, and is particularly pronounced in models of accelerated aging. We show that strengthening of the Ectodysplasin-A2-Receptor signalling axis in myogenic precursors and differentiated myotubes suffices to trigger potent parainflammatory responses, mirroring aspects of aging-driven sarcopenia. Intriguingly, obesity, insulin-resistance, and aging-related comorbidities, such as type-2-diabetes, result in heightened levels of the Ectodysplasin-A2 ligand. Our findings suggest that targeting the Ectodysplasin-A2 surface receptor represents a promising pharmacological strategy to mitigate the development of aging-associated phenotypes.
  • SARS-CoV-2 Entry Can Be Mimicked in C. elegans Expressing Human ACE2: A New Tool for Pharmacological Studies
    Margherita Romeo, Sara Baroni, Maria Monica Barzago, Samuela Gambini, Ada De Luigi, Daniela Iaconis, Andrea Rosario Beccari, Maddalena Fratelli, Luisa Diomede
    Viruses, 2025
    Testing medical countermeasures for SARS-CoV-2 transmission using vertebrates can be hindered by legislation regulating animal experimentation, high costs, and ethical concerns. To overcome these challenges, we propose a new Caenorhabditis elegans strain that constitutively expresses the human angiotensin-converting enzyme 2 receptor (ACE2). This resulted in significant impairment of reproduction and a defect in pharyngeal function compared to wild-type (WT) worms. SARS-CoV-2 infection was simulated by treating worms with the receptor-binding domain (RBD) of the spike protein, which caused dose-dependent and time-dependent pharyngeal impairment in ACE2 worms but not in WT worms. The toxicity of RBD was prevented by administering an anti-human ACE2 antibody, demonstrating that interactions with the ACE2 receptor are essential. The ACE2-expressing worm strain was further used for pharmacological research with Raloxifene. In vitro, 1–3 μM of Raloxifene reduced the entry of lentiviral particles carrying the Wuhan variant and B.1.1.7 UK and B.1.1.529 Omicron strains into HEK293-ACE2, in addition to particles expressing N501Y-mutated or P681H-mutated spike proteins. Raloxifene (0.1–1 μM) completely counteracted RBD toxicity in ACE2 worms, indicating that this strain offers a cost-effective in vivo screening platform for molecules with effects involving interactions with the ACE2 receptor.
  • Modeling immunoglobulin light chain amyloidosis in Caenorhabditis elegans
    Margherita Romeo, Maria Monica Barzago, Alessandro Corbelli, Silvia Maglioni, Natascia Ventura, Carmina Natale, Andrea Conz, Mario Salmona, Giovanni Palladini, Mario Nuvolone, Fabio Fiordaliso, Giampaolo Merlini, Luisa Diomede
    Dmm Disease Models and Mechanisms, 2025
    Cardiomyopathy determines the prognosis of patients with immunoglobulin light chain (AL) amyloidosis, a rare systemic disease caused by the misfolding and deposition of monoclonal light chains (LCs). The reasons underlying their cardiac tropism remain unknown, and an animal model recapitulating the main pathological features of AL amyloidosis is needed. Taking advantage of the similarities between the vertebrate cardiac muscle and Caenorhabditis elegans pharynx, we developed a new transgenic nematode expressing a human amyloidogenic λ LC, the sequence of which was deduced from a patient with AL amyloidosis with cardiac involvement (MNH). Strains expressing a non-amyloidogenic LC (MNM) or the empty vector only (MNV) were generated as controls. At variance with controls, LCs expressed in the body-wall muscle of MNH worms formed soluble dimeric assemblies, which could be secreted and reach different organs. Notably, MNH worms exerted a pharyngeal impairment resembling cardiac functional dysfunction in patients with AL amyloidosis, accompanied by increased radical oxygen species production and tissue ultrastructural damage. This new animal model could help to elucidate the mechanisms underlying the cardiac-specific toxicity occurring in AL amyloidosis, providing innovative insights into the pathophysiology.
  • Nanobodies Counteract the Toxicity an Amyloidogenic Light Chain by Stabilizing a Partially Open Dimeric Conformation
    Luca Broggini, Maria Monica Barzago, Valentina Speranzini, Tim Schulte, Federica Sonzini, Matteo Giono, Margherita Romeo, Paolo Milani, Serena Caminito, Giulia Mazzini, Paola Rognoni, Giampaolo Merlini, Carlo Pappone, Luigi Anastasia, Mario Nuvolone, Giovanni Palladini, Luisa Diomede, Stefano Ricagno
    Journal of Molecular Biology, 2023
  • Antitumour drugs targeting tau R3 VQIVYK and Cys322 prevent seeding of endogenous tau aggregates by exogenous seeds
    Narendran Annadurai, Lukáš Malina, Mario Salmona, Luisa Diomede, Antonio Bastone, Alfredo Cagnotto, Margherita Romeo, Martin Šrejber, Karel Berka, Michal Otyepka, Marián Hajdúch, Viswanath Das
    FEBS Journal, 2022
    Emerging experimental evidence suggests tau pathology spreads between neuroanatomically connected brain regions in a prion‐like manner in Alzheimer's disease (AD). Tau seeding, the ability of prion‐like tau to recruit and misfold naïve tau to generate new seeds, is detected early in human AD brains before the development of major tau pathology. Many antitumour drugs have been reported to confer protection against neurodegeneration, supporting the repurposing of approved and experimental or investigational oncology drugs for AD therapy. In this study, we evaluated whether antitumour drugs that abrogate the generation of seed‐competent aggregates of tau Repeat 3 (R3) domain peptides can prevent tau seeding and toxicity in Tau‐RD P301S FRET Biosensor cells and Caenorhabditis elegans. We demonstrate that drugs that interact with the N‐terminal VQIVYK or the C‐terminal region housing the Cys322 prevent R3 dimerisation, abolishing the generation of prion‐like R3 seeds. Preformed R3 seeds (fibrils) capped with, or R3 seeds formed in the presence of VQIVYK‐ or Cys322‐targeting drugs have a reduced potency to cause aggregation of naïve tau in biosensor cells and protect worms from aggregate toxicity. These findings indicate that VQIVYK‐ or Cys322‐targeting drugs may act as prophylactic agents against tau seeding.
  • Aryl Hydrocarbon Receptor-Dependent and-Independent Pathways Mediate Curcumin Anti-Aging Effects
    Vanessa Brinkmann, Margherita Romeo, Lucie Larigot, Anne Hemmers, Lisa Tschage, Jennifer Kleinjohann, Alfonso Schiavi, Swantje Steinwachs, Charlotte Esser, Ralph Menzel, Sara Giani Tagliabue, Laura Bonati, Fiona Cox, Niloofar Ale-Agha, Philipp Jakobs, Joachim Altschmied, Judith Haendeler, Xavier Coumoul, Natascia Ventura
    Antioxidants, 2022
    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor whose activity can be modulated by polyphenols, such as curcumin. AhR and curcumin have evolutionarily conserved effects on aging. Here, we investigated whether and how the AhR mediates the anti-aging effects of curcumin across species. Using a combination of in vivo, in vitro, and in silico analyses, we demonstrated that curcumin has AhR-dependent or -independent effects in a context-specific manner. We found that in Caenorhabditis elegans, AhR mediates curcumin-induced lifespan extension, most likely through a ligand-independent inhibitory mechanism related to its antioxidant activity. Curcumin also showed AhR-independent anti-aging activities, such as protection against aggregation-prone proteins and oxidative stress in C. elegans and promotion of the migratory capacity of human primary endothelial cells. These AhR-independent effects are largely mediated by the Nrf2/SKN-1 pathway.
  • Cu(II) Binding Increases the Soluble Toxicity of Amyloidogenic Light Chains
    Rosaria Russo, Margherita Romeo, Tim Schulte, Martina Maritan, Luca Oberti, Maria Monica Barzago, Alberto Barbiroli, Carlo Pappone, Luigi Anastasia, Giovanni Palladini, Luisa Diomede, Stefano Ricagno
    International Journal of Molecular Sciences, 2022
    Light chain amyloidosis (AL) is caused by the aberrant overproduction of immunoglobulin light chains (LCs). The resulting abnormally high LC concentrations in blood lead to deposit formation in the heart and other target organs. Organ damage is caused not only by the accumulation of bulky amyloid deposits, but extensive clinical data indicate that circulating soluble LCs also exert cardiotoxic effects. The nematode C. elegans has been validated to recapitulate LC soluble toxicity in vivo, and in such a model a role for copper ions in increasing LC soluble toxicity has been reported. Here, we applied microscale thermophoresis, isothermal calorimetry and thermal melting to demonstrate the specific binding of Cu2+ to the variable domain of amyloidogenic H7 with a sub-micromolar affinity. Histidine residues present in the LC sequence are not involved in the binding, and yet their mutation to Ala reduces the soluble toxicity of H7. Copper ions bind to and destabilize the variable domains and induce a limited stabilization in this domain. In summary, the data reported here, elucidate the biochemical bases of the Cu2+-induced toxicity; moreover, they also show that copper binding is just one of the several biochemical traits contributing to LC soluble in vivo toxicity.
  • Machine learning analyses of antibody somatic mutations predict immunoglobulin light chain toxicity
    Maura Garofalo, Luca Piccoli, Margherita Romeo, Maria Monica Barzago, Sara Ravasio, Mathilde Foglierini, Milos Matkovic, Jacopo Sgrignani, Raoul De Gasparo, Marco Prunotto, Luca Varani, Luisa Diomede, Olivier Michielin, Antonio Lanzavecchia, Andrea Cavalli
    Nature Communications, 2021
    In systemic light chain amyloidosis (AL), pathogenic monoclonal immunoglobulin light chains (LC) form toxic aggregates and amyloid fibrils in target organs. Prompt diagnosis is crucial to avoid permanent organ damage, but delayed diagnosis is common because symptoms usually appear only after strong organ involvement. Here we present LICTOR, a machine learning approach predicting LC toxicity in AL, based on the distribution of somatic mutations acquired during clonal selection. LICTOR achieves a specificity and a sensitivity of 0.82 and 0.76, respectively, with an area under the receiver operating characteristic curve (AUC) of 0.87. Tested on an independent set of 12 LCs sequences with known clinical phenotypes, LICTOR achieves a prediction accuracy of 83%. Furthermore, we are able to abolish the toxic phenotype of an LC by in silico reverting two germline-specific somatic mutations identified by LICTOR, and by experimentally assessing the loss of in vivo toxicity in a Caenorhabditis elegans model. Therefore, LICTOR represents a promising strategy for AL diagnosis and reducing high mortality rates in AL.
  • C. elegans detects toxicity of traumatic brain injury generated tau
    Elisa R. Zanier, Maria Monica Barzago, Gloria Vegliante, Margherita Romeo, Elena Restelli, Ilaria Bertani, Carmina Natale, Luca Colnaghi, Laura Colombo, Luca Russo, Edoardo Micotti, Luana Fioriti, Roberto Chiesa, Luisa Diomede
    Neurobiology of Disease, 2021
    in the long-term consequences of TBI. It also sets the groundwork for the development of a C. elegans-based platform for screening anti-tau compounds.
  • Antioxidant and anti‐inflammaging ability of prune (Prunus spinosa l.) extract result in improved wound healing efficacy
    Sofia Coppari, Mariastella Colomba, Daniele Fraternale, Vanessa Brinkmann, Margherita Romeo, Marco Bruno Luigi Rocchi, Barbara Di Giacomo, Michele Mari, Loretta Guidi, Seeram Ramakrishna, Natascia Ventura, Maria Cristina Albertini
    Antioxidants, 2021
  • An across-species comparison of the sensitivity of different organisms to Pb-based perovskites used in solar cells
    Guiyin Wang, Yujia Zhai, Shirong Zhang, Luisa Diomede, Paolo Bigini, Margherita Romeo, Sebastien Cambier, Servane Contal, Nhung H.A. Nguyen, Petra Rosická, Alena Ševců, Carmen Nickel, Martina G. Vijver, Willie J.G.M. Peijnenburg
    Science of the Total Environment, 2020
  • Inherent Biophysical Properties Modulate the Toxicity of Soluble Amyloidogenic Light Chains
    Martina Maritan, Margherita Romeo, Luca Oberti, Pietro Sormanni, Masayoshi Tasaki, Rosaria Russo, Arianna Ambrosetti, Paolo Motta, Paola Rognoni, Giulia Mazzini, Alberto Barbiroli, Giovanni Palladini, Michele Vendruscolo, Luisa Diomede, Martino Bolognesi, Giampaolo Merlini, Francesca Lavatelli, Stefano Ricagno
    Journal of Molecular Biology, 2020
  • Modulating the cardiotoxic behaviour of immunoglobulin light chain dimers through point mutations
    Martina Maritan, Arianna Ambrosetti, Luca Oberti, Alberto Barbiroli, Luisa Diomede, Margherita Romeo, Francesca Lavatelli, Pietro Sormanni, Giovanni Palladini, Martino Bolognesi, Giampaolo Merlini, Stefano Ricagno
    Amyloid, 2019
  • Methacycline displays a strong efficacy in reducing toxicity in a SCA3 Caenorhabditis elegans model
    Loredana Amigoni, Cristina Airoldi, Antonino Natalello, Margherita Romeo, Luisa Diomede, Paolo Tortora, Maria Elena Regonesi
    Biochimica Et Biophysica Acta General Subjects, 2019
  • V363I and V363A mutated tau affect aggregation and neuronal dysfunction differently in C. elegans
    Federica Morelli, Margherita Romeo, Maria Monica Barzago, Marco Bolis, Davide Mattioni, Giacomina Rossi, Fabrizio Tagliavini, Antonio Bastone, Mario Salmona, Luisa Diomede
    Neurobiology of Disease, 2018
  • Safety and Toxicology of Magnolol and Honokiol
    Andrea Sarrica, Natalja Kirika, Margherita Romeo, Mario Salmona, Luisa Diomede
    Planta Medica, 2018
  • HIV-1 matrix protein p17 misfolding forms toxic amyloidogenic assemblies that induce neurocognitive disorders
    Yasmin Zeinolabediny, Francesca Caccuri, Laura Colombo, Federica Morelli, Margherita Romeo, Alessandro Rossi, Silvia Schiarea, Carlotta Ciaramelli, Cristina Airoldi, Ria Weston, Liu Donghui, Jerzy Krupinski, Rubén Corpas, Elisa García-Lara, Sara Sarroca, Coral Sanfeliu, Mark Slevin, Arnaldo Caruso, Mario Salmona, Luisa Diomede
    Scientific Reports, 2017
  • Cardiac Light Chain Amyloidosis: The Role of Metal Ions in Oxidative Stress and Mitochondrial Damage
    Luisa Diomede, Margherita Romeo, Paola Rognoni, Marten Beeg, Claudia Foray, Elena Ghibaudi, Giovanni Palladini, Robert A. Cherny, Laura Verga, Gian Luca Capello, Vittorio Perfetti, Fabio Fiordaliso, Giampaolo Merlini, Mario Salmona
    Antioxidants and Redox Signaling, 2017
  • Inhibition of Aβ Amyloid Growth and Toxicity by Silybins: The Crucial Role of Stereochemistry
    Michele. F. M. Sciacca, Valeria Romanucci, Armando Zarrelli, Irene Monaco, Fabio Lolicato, Natalia Spinella, Clelia Galati, Giuseppe Grasso, Luisa D’Urso, Margherita Romeo, Luisa Diomede, Mario Salmona, Corrado Bongiorno, Giovanni Di Fabio, Carmelo La Rosa, Danilo Milardi
    ACS Chemical Neuroscience, 2017
  • Humanin Specifically Interacts with Amyloid-β Oligomers and Counteracts Their in vivo Toxicity
    Margherita Romeo, Matteo Stravalaci, Marten Beeg, Alessandro Rossi, Fabio Fiordaliso, Alessandro Corbelli, Mario Salmona, Marco Gobbi, Alfredo Cagnotto, Luisa Diomede
    Journal of Alzheimer S Disease, 2017
  • The new β amyloid-derived peptide Aβ1-6A2V-TAT(D) prevents Aβ oligomer formation and protects transgenic C. elegans from Aβ toxicity
    Luisa Diomede, Margherita Romeo, Alfredo Cagnotto, Alessandro Rossi, Marten Beeg, Matteo Stravalaci, Fabrizio Tagliavini, Giuseppe Di Fede, Marco Gobbi, Mario Salmona
    Neurobiology of Disease, 2016
  • Clusterin binds to Aβ1-42 Oligomers with high affinity and interferes with peptide aggregation by inhibiting primary and secondary nucleation
    Marten Beeg, Matteo Stravalaci, Margherita Romeo, Arianna Dorotea Carrá, Alfredo Cagnotto, Alessandro Rossi, Luisa Diomede, Mario Salmona, Marco Gobbi
    Journal of Biological Chemistry, 2016
  • SPIRE, a modular pipeline for eQTL analysis of RNA-Seq data, reveals a regulatory hotspot controlling miRNA expression in: C. elegans
    Ivan Kel, Zisong Chang, Nadia Galluccio, Margherita Romeo, Stefano Beretta, Luisa Diomede, Alessandra Mezzelani, Luciano Milanesi, Christoph Dieterich, Ivan Merelli
    Molecular Biosystems, 2016
  • Multigram synthesis and in Vivo efficacy studies of a novel multitarget anti-alzheimer's compound
    Irene Sola, Elisabet Viayna, Tània Gómez, Carles Galdeano, Matteo Cassina, Pelayo Camps, Margherita Romeo, Luisa Diomede, Mario Salmona, Pilar Franco, Mireille Schaeffer, Diego Colantuono, David Robin, Daniela Brunner, Nicole Taub, Birgit Hutter-Paier, Diego Muñoz-Torrero
    Molecules, 2015
  • A Caenorhabditis elegans-based assay recognizes immunoglobulin light chains causing heart amyloidosis
    Luisa Diomede, Paola Rognoni, Francesca Lavatelli, Margherita Romeo, Elena del Favero, Laura Cantù, Elena Ghibaudi, Andrea di Fonzo, Alessandro Corbelli, Fabio Fiordaliso, Giovanni Palladini, Veronica Valentini, Vittorio Perfetti, Mario Salmona, Giampaolo Merlini
    Blood, 2014
  • Soil quality in the Lomellina area using in vitro models and ecotoxicological assays
    Diego Baderna, Andrea Colombo, Margherita Romeo, Felice Cambria, Federico Teoldi, Marco Lodi, Luisa Diomede, Emilio Benfenati
    Environmental Research, 2014
  • Expression of A2V-mutated Aβ in Caenorhabditis elegans results in oligomer formation and toxicity
    Luisa Diomede, Giuseppe Di Fede, Margherita Romeo, Renzo Bagnati, Roberta Ghidoni, Fabio Fiordaliso, Monica Salio, Alessandro Rossi, Marcella Catania, Anna Paterlini, Luisa Benussi, Antonio Bastone, Matteo Stravalaci, Marco Gobbi, Fabrizio Tagliavini, Mario Salmona
    Neurobiology of Disease, 2014
  • Oleuropein Aglycone Protects Transgenic C. elegans Strains Expressing Aβ42 by Reducing Plaque Load and Motor Deficit
    Luisa Diomede, Stefania Rigacci, Margherita Romeo, Massimo Stefani, Mario Salmona
    Plos One, 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
  • Good gene, bad gene: New APP variant may be both
    Giuseppe Di Fede, Marcella Catania, Michela Morbin, Giorgio Giaccone, Maria Luisa Moro, Roberta Ghidoni, Laura Colombo, Massimo Messa, Alfredo Cagnotto, Margherita Romeo, Matteo Stravalaci, Luisa Diomede, Marco Gobbi, Mario Salmona, Fabrizio Tagliavini
    Progress in Neurobiology, 2012