Biochemistry, Genetics and Molecular Biology, Molecular Medicine, Molecular Biology
7
Scopus Publications
Scopus Publications
Comparative analysis reveals distinct metal and inflammatory cytokine profiles in the cerebrospinal fluid of children with neurological disorders Debora Curci, Martina Franzin, Enrico Pobega, Stefania Braidotti, Anna Flamigni, Gilda Paternuosto, Giulia Schillani, Riccardo Addobbati, Stefania Norbedo, Natalia Maximova Frontiers in Toxicology, 2026 Introduction The adverse effect of metals and metalloids on neural development is a significant health concern, especially in vulnerable populations, such as pediatric patients. Excessive accumulation of these elements in the developing central nervous system (CNS) can induce oxidative stress, trigger cell death, and promote neuroinflammation. However, few studies have quantified metal and metalloid concentrations in cerebrospinal fluid (CSF) in pediatric patients, and, to our knowledge, none have compared these levels between children with and without neurological disorders. Methods In this exploratory study, we compared pediatric patients with neurological diseases or CNS infections to control pediatric patients to assess differences in metal and metalloid concentrations and in CSF inflammatory cytokine profiles. Results We observed higher levels of most metals and metalloids in neurological and infection patients, while group-specific differences were observed in cytokines. Notably, the cytokines Pentraxin-3 and IL-8 showed positive correlations with calcium, copper, iron, antimony, and chromium, suggesting a possible functional relationship in neuroinflammation. Discussion In conclusion, this study presents a comparative analysis of CSF metal and metalloid levels in conjunction with inflammatory cytokine profiles in a pediatric population, providing a basis for further research into their roles in neuroinflammation and neurological disease.
Unveiling the unfolded proteome: Evaluation and comparison of methods for the enrichment of intrinsically disordered proteins Luca Secco, Giulia Rocca, Alberto Maria Davide Ingo, Enrico Pobega, Valentina Laera, Guidalberto Manfioletti, Giorgio Arrigoni, Riccardo Sgarra Protein Science, 2026 Intrinsically disordered proteins (IDPs) represent a family of proteins that given their structural peculiarity, that is, absence of defined secondary or tertiary structures, are very flexible and display great adaptability in binding to other molecules. For these reasons, IDPs are often key nodes in modulatory molecular networks. While 3D‐structured proteins undergo aggregation and precipitation in denaturing conditions, due to the exposure of their hydrophobic core to the aqueous environment, IDPs are instead refractory to aggregation due to their naturally disordered state. This peculiarity has prompted the use of harsh conditions (i.e., heat or low pH) to selectively extract IDPs from complex protein samples. Here we provide the first comprehensive comparison and evaluation of the two strategies commonly adopted to enrich for IDPs, that is, heat‐ and perchloric acid‐based extractions. We find that both methods allow the study of the intrinsically disordered “dark side” of the proteome, while displaying acute differences in their ability to enrich these peculiar IDPs.
Identification of a new small Rho GTPase inhibitor effective in glioblastoma human cells Angela Parise, Ivana Manini, Enrico Pobega, Sonia Covaceuszach, Luca Secco, Federica Simonelli, Serena Mastantuono, Carla di Loreto, Alessio Pizzignach, Miran Skrap, Marco Vindigni, Riccardo Sgarra, Guidalberto Manfioletti, Daniela Cesselli, Alessandra Magistrato European Journal of Medicinal Chemistry, 2025
Imaging the Response to DNA Damage in Heterochromatin Domains Audrey Chansard, Enrico Pobega, Pierre Caron, Sophie E. Polo Frontiers in Cell and Developmental Biology, 2022 The eukaryotic genome is assembled in a nucleoprotein complex called chromatin, whose organization markedly influences the repair of DNA lesions. For instance, compact chromatin states, broadly categorized as heterochromatin, present a challenging environment for DNA damage repair. Through transcriptional silencing, heterochromatin also plays a vital role in the maintenance of genomic integrity and cellular homeostasis. It is thus of critical importance to decipher whether and how heterochromatin affects the DNA damage response (DDR) to understand how this chromatin state is preserved after DNA damage. Here, we present two laser micro-irradiation-based methods for imaging the DDR in heterochromatin domains in mammalian cells. These methods allow DNA damage targeting to specific subnuclear compartments, direct visualization of the DDR and image-based quantification of the repair response. We apply them to study DNA double-strand break repair pathways in facultative heterochromatin and the repair of UV photoproducts in constitutive heterochromatin. We discuss the advantages and limitations of these methods compared to other targeted approaches for DNA damage induction.
DNA Double-Strand Break Repair: All Roads Lead to HeterochROMAtin Marks Pierre Caron, Enrico Pobega, Sophie E. Polo Frontiers in Genetics, 2021 In response to DNA double-strand breaks (DSBs), chromatin modifications orchestrate DNA repair pathways thus safeguarding genome integrity. Recent studies have uncovered a key role for heterochromatin marks and associated factors in shaping DSB repair within the nucleus. In this review, we present our current knowledge of the interplay between heterochromatin marks and DSB repair. We discuss the impact of heterochromatin features, either pre-existing in heterochromatin domains or de novo established in euchromatin, on DSB repair pathway choice. We emphasize how heterochromatin decompaction and mobility further support DSB repair, focusing on recent mechanistic insights into these processes. Finally, we speculate about potential molecular players involved in the maintenance or the erasure of heterochromatin marks following DSB repair, and their implications for restoring epigenome function and integrity.
The high mobility group A1 (HMGA1) chromatin architectural factor modulates nuclear stiffness in breast cancer cells Beatrice Senigagliesi, Carlotta Penzo, Luisa Ulloa Severino, Riccardo Maraspini, Sara Petrosino, Hernan Morales-Navarrete, Enrico Pobega, Elena Ambrosetti, Pietro Parisse, Silvia Pegoraro, Guidalberto Manfioletti, Loredana Casalis, Riccardo Sgarra International Journal of Molecular Sciences, 2019 Plasticity is an essential condition for cancer cells to invade surrounding tissues. The nucleus is the most rigid cellular organelle and it undergoes substantial deformations to get through environmental constrictions. Nuclear stiffness mostly depends on the nuclear lamina and chromatin, which in turn might be affected by nuclear architectural proteins. Among these is the HMGA1 (High Mobility Group A1) protein, a factor that plays a causal role in neoplastic transformation and that is able to disentangle heterochromatic domains by H1 displacement. Here we made use of atomic force microscopy to analyze the stiffness of breast cancer cellular models in which we modulated HMGA1 expression to investigate its role in regulating nuclear plasticity. Since histone H1 is the main modulator of chromatin structure and HMGA1 is a well-established histone H1 competitor, we correlated HMGA1 expression and cellular stiffness with histone H1 expression level, post-translational modifications, and nuclear distribution. Our results showed that HMGA1 expression level correlates with nuclear stiffness, is associated to histone H1 phosphorylation status, and alters both histone H1 chromatin distribution and expression. These data suggest that HMGA1 might promote chromatin relaxation through a histone H1-mediated mechanism strongly impacting on the invasiveness of cancer cells.
