Partial Inhibition Of Nampt Restores Metabolic Vulnerability And Synergizes With Anti-Myeloma Agents In Multiple Myeloma Giulia Giorgetti Haematologica, 2026 Introduction. Multiple myeloma (MM) is a metabolically demanding plasma cell malignancy in which resistance to current therapies remains a major clinical challenge. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the NAD⁺ salvage pathway, sustains cellular energetics and redox balance in tumor cells and is frequently upregulated in MM. We previously reported that complete inhibition of NAMPT disrupts NAD⁺ metabolism in malignant and normal cells, leading to dose-limiting toxicities that have hindered clinical development. RPT1F is a novel, first-in-class partial NAMPT inhibitor designed to preserve residual enzymatic activity in healthy cells while selectively disrupting NAD⁺ homeostasis in tumor cells. This study aimed to evaluate the efficacy and mechanistic synergy of RPT1F, alone and in combination with standard anti-MM agents, in preclinical models.Methods. RPT1F was first tested on bone marrow mononuclear cells collected from MM patients to assess selective toxicity toward malignant plasma cells (CD138⁺) versus normal immune subsets (CD138⁻), including NK, NKT, B lymphocytes, and CD8⁺/CD4⁺ T cells. Anti-tumor activity was then evaluated across a panel of genetically and metabolically heterogeneous MM cell lines. Cell viability, apoptosis, NAD⁺/ATP levels, and mitochondrial oxygen consumption rate (OCR) were quantified after 24-hour drug exposure. Combination studies with clinically used anti-MM drugs were performed, and drug synergy was analyzed using Bliss independence modeling.Results. RPT1F induced a dose-dependent reduction in NAMPT activity and NAD⁺ levels, leading to marked disruption of bioenergetic homeostasis in MM cells but not in normal immune cells, where metabolic reserve-maintained viability. Strong anti-myeloma activity was observed across all tested cell lines, irrespective of cytogenetic background. Combination of RPT1F with standard agents produced synergistic cytotoxicity characterized by enhanced oxidative stress and impaired antioxidant defenses.Conclusions. Partial inhibition of NAMPT with RPT1F offers a novel and safer approach to targeting NAD⁺ metabolism in multiple myeloma. The combination of RPT1F with different anti-myeloma drugs effectively overcomes apoptotic and metabolic resistance mechanisms, resulting in selective tumor killing without affecting normal cells. These findings support the clinical development of RPT1F based regimens, particularly in metabolically adaptive or drug-resistant MM, and provide a strong rationale for future phase I trials in relapsed/refractory disease.
The pivotal role of endoplasmic reticulum in cancer glucose metabolism Cecilia Marini, Maddalena Ghelardoni, Sonia Carta, Tiziana Bachetti, Silvia Bruno, Isotta Cainero, Silvia Ravera, Roberto Benelli, Marco Scotto, Francesca Vitale, Santina Bruzzone, Serena Losacco, Sabrina Chiesa, Matteo Bauckneht, Gabriele Tancreda, Matteo Raineri, Anna Maria Orengo, Andrea Benzi, Gianmario Sambuceti Iscience, 2026 silencing) and hydrolysis (by silencing glucose-6-phosphatase) eventually results in a measurable ER collapse documenting the high-rate nature of G6P flux across the reticular membrane.
From Bench to Clinic: The 2024 FASEB Scientific Research Conference on NAD Metabolism and Signaling Shin-ichiro Imai, Eija Pirinen, Michael N. Sack, Jonas T. Treebak, Charalampos Tzoulis, Santina Bruzzone, Andreas H. Guse, Michael O. Hottiger, Xiaolu A. Cambronne Molecular Medicine, 2025 The 2024 FASEB Scientific Research Conference on NAD Metabolism and Signaling was held in Lisbon, Portugal and served to (1) unite researchers, clinicians, and trainees, (2) create opportunities for early-stage investigators by showcasing their work on an international stage and promote collaborations, (3) train the next generation of scientists in the field, and (4) improve human health by furthering our understanding of NAD + metabolism and signaling. With the burgeoning potential of NAD + as a therapeutic agent for multiple health conditions, as well as many remaining scientific questions about the NAD + metabolome, an expert panel discussion titled “NAD + Health Outcomes Forum: A Call to Action” was hosted on Thursday, August 29, 2024. The main objectives were to discuss and translate what is known about NAD + biology into tangible actions and to identify what remains unknown into a research call to action. Given the broad and reaching impact of NAD + on health, there is significant interest in NAD + pathway modulation, including through precursors such as nicotinic acid, nicotinamide (NAM), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). There is also growing research regarding the heterogeneity among individuals, as well as differences and similarities among the NAD + precursors, specifically in relation to dosing, timing, and their impact on various health conditions.
CD56 expression modulates NAD+ metabolic landscape and predicts sensitivity to anti-CD38 therapies in multiple myeloma Giulia Giorgetti, Elena Maroto-Martin, Debora Soncini, Daniela Fenoglio, Pamela Becherini, Andrea Benzi, Silvia Ravera, Isabella Traverso, Francesco Ladisa, Francesco Lai, Giulia Rivoli, Dario Truffelli, Aimable Nahimana, Antonia Cagnetta, Fabio Guolo, Chiara R. M. Uras, Anaïs Schavgoulidze, Jessica Fong Ng, Alessio Nencioni, Santina Bruzzone, Nikhil C. Munshi, Roberto Massimo Lemoli, Mariateresa Fulciniti, Michele Cea Blood Cancer Journal, 2025 In multiple myeloma (MM), monoclonal antibodies targeting CD38, such as Daratumumab (Dara) and Isatuximab (Isa), are standard-of-care drugs that produce good responses. However, it is likely that some patients will become resistant even to these innovative therapies. Recently, Robinette et al. [ 1 ] reported that CD56 levels on bone marrow plasma cells (BMPCs) predict the efficacy of Dara-based regimens, especially when combined with immunomodulatory drugs [ 2 ]. CD56, also known as NCAM1 (Neural Cell Adhesion Molecule 1), facilitates cell-cell adhesion and is deregulated in many tumors, including MM [ 3 ].
Harnessing metabolic control for synaptic stability: REST/NRSF links glycolytic inhibition to excitatory neurotransmission Daniele Ferrante, Barbara Parisi, Antonella Marte, Dionisi Marianna, Cosimo Prestigio, Andrea Benzi, Santina Bruzzone, Fabio Benfenati, Franco Onofri, Pierluigi Valente, Pietro Baldelli Journal of Physiology, 2025 Under resting conditions most neuronal ATP is produced through mitochondrial oxidative phosphorylation, whereas glycolysis becomes more important during intense neuronal firing. Recent studies suggest that inhibiting glycolysis plays a key role in regulating seizure‐related hyperactivity, with the epigenetic modulator REST/NRSF being activated when glycolysis inhibition lowers the NADH/NAD+ ratio. Our previous research has shown that REST/NRSF initiates homeostatic processes to counteract neuronal hyperactivity by regulating both firing and synaptic activities. However, the exact mechanism through which the metabolic activation of REST/NRSF controls neuronal excitability is still unknown. Here, we studied the role of REST/NRSF in the effects of glycolysis inhibition on hippocampal neuron activity. Treatment with 2‐deoxy‐d‐glucose (2DG) decreased the NADH/NAD+ ratio, increased REST/NRSF expression, and promoted its nuclear translocation. Although GABAergic inhibitory inputs and the firing properties of both excitatory and inhibitory neurons were unaffected by 2DG, the amplitude of evoked EPSCs (eEPSCs) and miniature EPSCs (mEPSCs) was reduced in a REST/NRSF‐dependent manner. This effect was associated with a REST/NRSF‐dependent reduction in the size of GluA2‐positive puncta and a decrease in GluA2 expression in the absence of changes in the density of excitatory synapses. These effects provide a mechanistic basis for the significant reduction in network firing and bursting activity observed when the hippocampal network was treated with 2DG. These findings highlight a role of the REST/NRSF‐dependent pathway in the 2DG‐mediated downregulation of excitatory inputs, a mechanism that contributes to neuronal network stability, strengthening the homeostatic defences against hyperactivity. imageKey points Reducing glucose metabolism with 2‐deoxy‐d‐glucose (2DG) lowers the cell's energy balance and increases the levels of a gene regulator called REST/NRSF. REST/NRSF then moves into the nucleus, where it controls the activity of genes linked to nerve cell communication. 2DG weakens the strength of signals between excitatory nerve cells, without affecting inhibitory signals or the basic ability of neurons to fire. This effect depends in part on REST/NRSF, which reduces the amount and size of GluA2‐containing AMPA receptors at excitatory synapses, without altering the overall number of excitatory contacts. These findings suggest that blocking glucose metabolism activates a protective response that stabilizes brain networks, which could help control seizures in epilepsy.
Genetic Deletion of the Purinergic Receptor P2rx7 Worsens the Phenotype of α-Sarcoglycan Muscular Dystrophy Cecilia Astigiano, Elisa Principi, Sara Pintus, Andrea Benzi, Serena Baratto, Chiara Panicucci, Mario Passalacqua, Juan Sierra-Marquez, Annette Nicke, Francesca Antonini, Genny Del Zotto, Annunziata Gaetana Cicatiello, Lizzia Raffaghello, Tanja Rezzonico Jost, Fabio Grassi, Santina Bruzzone, Claudio Bruno, Elisabetta Gazzerro ACS Pharmacology and Translational Science, 2025 High Resolution Image Download MS PowerPoint Slide Limb-girdle muscular dystrophy R3 (LGMDR3), a rare genetic disorder characterized by progressive impairment of limb, diaphragmatic, and respiratory muscles, is caused by loss-of-function mutations in the α-sarcoglycan gene ( SGCA ) and aggravated by immune-mediated damage and fibrotic tissue replacement. Pharmacological inhibition of purinergic receptor P2X7 (P2X7R) reduced inflammation and fibrosis in Sgca –/– mice. To further define the role of P2X7R, we generated a double knockout mouse model Sgca –/– P2rx7 -/ - . We compared diaphragms isolated from 24-week-old Sgca –/– P2rx7 +/+ and Sgca –/– P2rx7 –/– mice since the diaphragmatic muscle is early and severely damaged by Sgca genetic loss-of-function. Unexpectedly, Sgca –/– P2rx7 –/– mice displayed increased extracellular matrix deposition and augmented cellularity in fibrotic areas, in particular, a higher number of CD3 + lymphocytes and Iba1 + macrophages compared to Sgca –/– P2rx7 +/+ mice. Moreover, intense P2X4R signal colocalized with CD3 + and Iba1 + cells, confirming its expression by these infiltrating immune cells. Absence of an improvement of the dystrophic phenotype was histologically confirmed in Sgca –/– P2rx7 –/– quadriceps, although the fibrotic reaction was milder than that in diaphragms, suggesting a differential influence of the tissue microenvironment on the receptor functions. Flow cytometric analysis of limb muscle-infiltrating immune cells revealed a decrease in NK cells. Motor performance tests did not reveal any difference between the two genotypes. In conclusion, this study identified a divergent outcome of genetic deletion of the P2rx7 gene as compared to P2X7R blockade in α-sarcoglycan dystrophic tissue, suggesting that pharmacological interventions targeting the P2X7R in dystrophic immune-mediated damage require careful definition of a precise time window and dosage.
Emerging strategies, applications and challenges of targeting NAD+ in the clinic Jianying Zhang, He-Ling Wang, Sofie Lautrup, Hilde Loge Nilsen, Jonas T. Treebak, Leiv Otto Watne, Geir Selbæk, Lindsay E. Wu, Torbjørn Omland, Eija Pirinen, Tin Cho Cheung, Jun Wang, Mathias Ziegler, Ole-Bjørn Tysnes, Rubén Zapata-Pérez, Santina Bruzzone, Carles Canto, Michela Deleidi, Georges E. Janssens, Riekelt H. Houtkooper, Morten Scheibye-Knudsen, Masaya Koshizaka, Koutaro Yokote, Eric Verdin, Vilhelm A. Bohr, Charalampos Tzoulis, David A. Sinclair, Evandro Fei Fang Nature Aging, 2025
NAD+ metabolism restriction boosts high-dose melphalan efficacy in patients with multiple myeloma Debora Soncini, Pamela Becherini, Francesco Ladisa, Silvia Ravera, Adithya Chedere, Elisa Gelli, Giulia Giorgetti, Claudia Martinuzzi, Francesco Piacente, Luca Mastracci, Claudia Veneziano, Gianluca Santamaria, Fiammetta Monacelli, Moustafa S. Ghanem, Antonia Cagnetta, Fabio Guolo, Matteo Garibotto, Sara Aquino, Mario Passalaqua, Santina Bruzzone, Axel Bellotti, Michel A. Duchosal, Aimable Nahimana, Emanuele Angelucci, Chandra Nagasuma, Alessio Nencioni, Roberto Massimo Lemoli, Michele Cea Blood Advances, 2025 Elevated levels of the NAD+-generating enzyme nicotinamide phosphoribosyltransferase (NAMPT) are a common feature across numerous cancer types. Accordingly, we previously reported pervasive NAD+ dysregulation in multiple myeloma (MM) cells in association with upregulated NAMPT expression. Unfortunately, albeit being effective in preclinical models of cancer, NAMPT inhibition has proven ineffective in clinical trials because of the existence of alternative NAD+ production routes using NAD+ precursors other than nicotinamide. Here, by leveraging mathematical modeling approaches integrated with transcriptome data, we defined the specific NAD+ landscape of MM cells and established that the Preiss-Handler pathway for NAD+ biosynthesis, which uses nicotinic acid as a precursor, supports NAD+ synthesis in MM cells via its key enzyme nicotinate phosphoribosyltransferase (NAPRT). Accordingly, we found that NAPRT confers resistance to NAD+-depleting agents. Transcriptomic, metabolic, and bioenergetic profiling of NAPRT-knockout (KO) MM cells showed these to have weakened endogenous antioxidant defenses, increased propensity to oxidative stress, and enhanced genomic instability. Concomitant NAMPT inhibition further compounded the effects of NAPRT-KO, effectively sensitizing MM cells to the chemotherapeutic drug, melphalan; NAPRT added-back fully rescues these phenotypes. Overall, our results propose comprehensive NAD+ biosynthesis inhibition, through simultaneously targeting NAMPT and NAPRT, as a promising strategy to be tested in randomized clinical trials involving transplant-eligible patients with MM, especially those with more aggressive disease.
Editorial: Adenine nucleotides in immunity and inflammation Christa E. Müller, Santina Bruzzone, Andreas H. Guse Frontiers in Immunology, 2025 Intracellular signaling encompasses two larger areas, Ca 2+ signaling evoked or modulated by AN, or signaling by the intracellular 2 nd messenger 3',5'-cyclic adenosine monophosphate (cAMP). Ca 2+ signaling o[en starts locally and, through several amplifica3on mechanisms, subsequently turns into global signaling. Ca 2+ microdomains are local Ca 2+ signals that can be observed by high-or super-resolu3on microscopy imaging techniques. A review by Gil Montoya et al. describes the use of mathema3cal modeling as a 'lens' to overcome the resolu3on restric3ons in modern microscopy through predic3on of AN-driven signaling processes (h\ps://doi.org/10.3389/fimmu.2023.1235737). Along these lines, an opensource Python pipeline for Ca 2+ microdomain off-line analysis is presented by Woelk et al. as a tool to serve the community (h\ps://doi.org/10.3389/fimmu.2023.1299435). A specific example of how AN differen3ally regulate even the same ca3on channel was discovered by Pick et al.; the authors describe kine3cs and current amplitudes of the non-selec3ve ca3on channel TRPM2 over a wide range of Ca 2+ concentra3ons, showing more rapid kine3cs and higher amplitudes for the TRPM2 superagonist 2'-deoxy-ADPR as compared to ADPR (h\ps://doi.org/10.3389/fimmu.2024.1294357).In addi3on to Ca 2+ signaling that is known to be essen3al for T cell ac3va3on, cAMP is currently rather considered a nega3ve intracellular regulator of T cell ac3va3on. Three papers are focused on the ATP-ac3vated pro-inflammatory P2X receptor subtypes P2X4 and/or P2X7, and their role on immune cells. Longo et al. discovered a crucial role of the P2X7 receptor for an3gen-specific T cell immunity in a viral infec3on model (h\ps://doi.org/10.3389/fimmu.2024.1360140). Sierra-Marquez et al. studied the localiza3on of P2X4 and P2X7 receptors in na3ve mouse lung; they found neither evidence for heteromeric P2X4/P2X7 receptors nor for direct interac3on of both receptor subtypes (h\ps://doi.org/10.3389/fimmu.2024.1425938). In a study by Brock et al., the role of P2X4 and P2X7 receptors during CD8 + T cell ac3va3on was inves3gated using 3me-resolved high-resolu3on imaging. The study demonstrated that P2X4 and P2X7 receptor signaling enhanced ini3al Ca 2+ events during CD8 + T cell ac3va3on and played a crucial role in regula3ng downstream responses, including NFAT-1 transloca3on, cytokine expression, and prolifera3on (h\ps://doi.org/10.3389/fimmu.2024.1258119).Extracellular AN are substrates of ectonucleo3dases, nucleo3de-metabolizing enzymes that are integrated into the cell membrane or a\ached to it. The enzymes can also be present in exosomes or as soluble enzymes in the extracellular fluid. They hydrolyze AN, cleaving phosphoric acid ester groups. Depending on the subtype, ectonucleo3dases convert AN to other AN, or form, at the end of the hydroly3c cascade, immunosuppressive, an3inflammatory adenosine. In their review ar3cle, Winzer et al. summarize the role of extracellular vesicles containing ectonucleo3dases and further purine-metabolizing enzymes involved in purinergic signaling (h\ps://doi.org/10.3389/fimmu.2024.1362996). An original ar3cle by Zubiar et al. focuses on the ectonucleo3dase CD38 (NADglycohydrolase, also displaying ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase enzyma3c ac3vi3es; CD, cluster of differen3a3on). CD38 deficiency in a mouse model of chronic gra[-versus-host disease resulted in an altered transcriptomic response to the induc3on of the disease. These results indicated an immunomodulatory and proinflammatory role of CD38 in the onset of this disease model (h\ps://doi.org/10.3389/fimmu.2025.1441981). Jaeckstein et al. studied the key ectonucleo3dase CD73 (ecto-5'-nucleo3dase), which catalyzes the hydrolysis of AMP to produce adenosine. U3lizing knockout mice deficient in vascular endothelial CD73 expression, they inves3gated the enzyme's role in the context of adipose 3ssue homeostasis (h\ps://doi.org/10.3389/fimmu.2023.1308456).Extracellular ATP, ADP, AMP, or NAD can be hydrolyzed by the orchestrated ac3on of ectonucleo3dases to finally produce adenosine, which triggers the ac3va3on of adenosine receptors (classified into four subtypes, A1, A2A, A2B, and A3). Extracellular adenosine regulates a broad range of physiological processes, including modula3on of the immune system, with adenosine being mostly known as an immunosuppressive agent. Wendlandt et al. demonstrated that the A2A adenosine receptors are present in astrocytes in the olfactory bulb, one of the brain regions that is first affected in neurodegenera3ve disorders. Ac3va3on of A2A adenosine receptors determines an increase in the intracellular cAMP concentra3on, both in control and in a mouse model of mul3ple sclerosis, indica3ng that A2A receptor-dependent pathways in olfactory bulb astrocytes are not affected by neuroinflamma3on (h\ps://doi.org/10.3389/fimmu.2023.1273837). Paladines et al. demonstrated that the an3-inflammatory ac3on exerted by extracellular adenosine in human gingival fibroblasts is mediated by the ac3va3on of A2A receptors and by subsequent triggering of the AMP kinase/Sirtuin 1/PGC-1α axis, with upregula3on of mitochondrial biogenesis, ul3mately regula3ng mitochondrial oxida3ve phosphoryla3on and metabolic energy produc3on (h\ps://doi.org/10.3389/fimmu.2023.1148216).Several research papers describe new methods and tools to study AN signaling as well as their targets involved in inflamma3on and immunity. Hiefner and colleagues developed a liquid chromatography-tandem mass spectrometrybased method for the quan3fica3on of AN and their degrada3on products (h\ps://doi.org/10.3389/fimmu.2023.1250762). Stamataki et al. present a review on novel adeno-associated viral vectors for the targe3ng of microglia: to develop more precise, specific and effec3ve interven3ons to modulate microglial behavior may represent a promising strategy to alt neuroinflamma3on (h\ps://doi.org/10.3389/fimmu.2024.1425892). Finally, Lopez and colleagues studied natural and synthe3c heparins as potent inhibitors of the AN-metabolizing enzyme ectonucleo3de pyrophosphatase/phosphodiesterase-1 (NPP1). They conclude that this mechanism of ac3on may contribute to the an3-cancer effects of heparins observed in some studies (h\ps://doi.org/10.3389/fimmu.2023.1173634).Besides being crucial in metabolic energy, AN represent pivotal mediators both as extracellular and intracellular signals. Both ATP or NAD release and their conversion by ectoenzymes to AMP/adenosine ac3vate purinergic receptor signaling. This and other signaling pathways are coupled to the intracellular genera3on of AN second messengers, regula3ng Ca 2+ homeostasis and cell responses. The exact understanding and defini3on of the molecular cascade governing physiological and pathological processes (inflamma3on, neurodegenera3on etc), as well as the characteriza3on of the expression of AN-degrading enzymes and AN-sensi3ve receptors in different condi3ons, may offer the possibility of developing therapeu3c strategy and/or of iden3fying new biomarkers (possibly also expressed on EV). This Research Topic presents interes3ng inputs covering different aspects of this mul3faceted AN-based signaling network.
Membrane IL-18 identifies a human macrophage subset with distinct proteomic and functional traits Chiara Vitale, Andrea Petretto, Katia Cortese, Sonia Carta, Alessandra Dondero, Chiara Lavarello, Davide Cangelosi, Martina Morini, Francesca Bellora, Pietro Arnaldi, Fabrizio Loiacono, Santina Bruzzone, Francesco Piacente, Silvia Bruno, Martina Serra, Annamaria Pessino, Serafina Mammoliti, Alberto Garaventa, Massimo Conte, Massimo Locati, Giuseppe Danilo Norata, Marco Colonna, Eric Vivier, Cristina Bottino, Roberta Castriconi Oncoimmunology, 2025 This study contributes to the characterization of human macrophages in normal and pathological conditions such as cancer. We characterized a macrophage population expressing membrane-associated IL-18 (mIL-18) that shows peculiar proteomic, phenotypic, ultrastructural, and functional properties. mIL-18+ macrophages exhibit increased levels of key proteins involved in pathogen recognition, activation, migration, and endocytosis. They also display specialized functions in vesicle and actin filament transport and lipid metabolism, and have typical mitochondrial traits. Importantly, mIL-18+ cells dominate the peritoneal fluid of adult cancer patients and are present in the bone marrow of children with neuroblastoma. They express high levels of TREM2 but display heterogeneous FOLR2 expression, distinguishing distinct cell subsets with possibly different functions. Accordingly, in primary neuroblastomas, transcriptional signatures associated with mIL-18 expression show different prognostic values. Our data show that mIL-18+ macrophages, which are predominant across the tumor microenvironment, exhibit previously undetected heterogeneity, potentially impacting tumor progression in a variable manner.
Sirtuin 6 Regulates the Activation of the ATP/Purinergic Axis in Endothelial Cells Cecilia Astigiano, Francesco Piacente, Maria Elena Laugieri, Andrea Benzi, Christian A. Di Buduo, Carolina P. Miguel, Debora Soncini, Michele Cea, Antonella Antonelli, Mauro Magnani, Alessandra Balduini, Antonio De Flora, Santina Bruzzone International Journal of Molecular Sciences, 2023
CD38-Induced Metabolic Dysfunction Primes Multiple Myeloma Cells for NAD+-Lowering Agents Pamela Becherini, Debora Soncini, Silvia Ravera, Elisa Gelli, Claudia Martinuzzi, Giulia Giorgetti, Antonia Cagnetta, Fabio Guolo, Federico Ivaldi, Maurizio Miglino, Sara Aquino, Katia Todoerti, Antonino Neri, Andrea Benzi, Mario Passalacqua, Alessio Nencioni, Ida Perrotta, Maria Eugenia Gallo Cantafio, Nicola Amodio, Antonio De Flora, Santina Bruzzone, Roberto M. Lemoli, Michele Cea Antioxidants, 2023
PLX4032 resistance of patient-derived melanoma cells: crucial role of oxidative metabolism Ombretta Garbarino, Giulia Elda Valenti, Lorenzo Monteleone, Gabriella Pietra, Maria Cristina Mingari, Andrea Benzi, Santina Bruzzone, Silvia Ravera, Riccardo Leardi, Emanuele Farinini, Stefania Vernazza, Melania Grottoli, Barbara Marengo, Cinzia Domenicotti Frontiers in Oncology, 2023
The TRPM2 ion channel regulates metabolic and thermogenic adaptations in adipose tissue of cold-exposed mice Andrea Benzi, Markus Heine, Sonia Spinelli, Annalisa Salis, Anna Worthmann, Björn Diercks, Cecilia Astigiano, Raúl Pérez Mato, Adela Memushaj, Laura Sturla, Valerio Vellone, Gianluca Damonte, Michelle Y. Jaeckstein, Friedrich Koch-Nolte, Hans-Willi Mittrücker, Andreas H. Guse, Antonio De Flora, Joerg Heeren, Santina Bruzzone Frontiers in Endocrinology, 2023
Structure-Based Identification and Biological Characterization of New NAPRT Inhibitors Jorge Franco, Francesco Piacente, Melanie Walter, Simone Fratta, Moustafa Ghanem, Andrea Benzi, Irene Caffa, Alexander V. Kurkin, Andrea Altieri, Patrick Herr, Macarena Martínez-Bailén, Inmaculada Robina, Santina Bruzzone, Alessio Nencioni, Alberto Del Rio Pharmaceuticals, 2022
Identification of NAPRT Inhibitors with Anti-Cancer Properties by In Silico Drug Discovery Moustafa S. Ghanem, Irene Caffa, Alberto Del Rio, Jorge Franco, Marco Daniele Parenti, Fiammetta Monacelli, Michele Cea, Amr Khalifa, Aimable Nahimana, Michel A. Duchosal, Silvia Ravera, Nadia Bertola, Santina Bruzzone, Alessio Nencioni, Francesco Piacente Pharmaceuticals, 2022
Nampt controls skeletal muscle development by maintaining Ca2+ homeostasis and mitochondrial integrity Astrid L. Basse, Marianne Agerholm, Jean Farup, Emilie Dalbram, Joachim Nielsen, Niels Ørtenblad, Ali Altıntaş, Amy M. Ehrlich, Thomas Krag, Santina Bruzzone, Morten Dall, Roldan M. de Guia, Jonas B. Jensen, Andreas B. Møller, Anders Karlsen, Michael Kjær, Romain Barrès, John Vissing, Steen Larsen, Niels Jessen, Jonas T. Treebak Molecular Metabolism, 2021
CD38 downregulation modulates NAD+ and NADP(H) levels in thermogenic adipose tissues Andrea Benzi, Laura Sturla, Markus Heine, Alexander W. Fischer, Sonia Spinelli, Mirko Magnone, Giovanna Sociali, Alessia Parodi, Daniela Fenoglio, Laura Emionite, Friedrich Koch-Nolte, Hans-Willi Mittrücker, Andreas H. Guse, Antonio De Flora, Elena Zocchi, Joerg Heeren, Santina Bruzzone Biochimica Et Biophysica Acta Molecular and Cell Biology of Lipids, 2021
Slc12a8 is a nicotinamide mononucleotide transporter Alessia Grozio, Kathryn F. Mills, Jun Yoshino, Santina Bruzzone, Giovanna Sociali, Kyohei Tokizane, Hanyue Cecilia Lei, Richard Cunningham, Yo Sasaki, Marie E. Migaud, Shin-ichiro Imai Nature Metabolism, 2019
Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody Karina Kaczmarek-Hajek, Jiong Zhang, Robin Kopp, Antje Grosche, Björn Rissiek, Anika Saul, Santina Bruzzone, Tobias Engel, Tina Jooss, Anna Krautloher, Stefanie Schuster, Tim Magnus, Christine Stadelmann, Swetlana Sirko, Friedrich Koch-Nolte, Volker Eulenburg, Annette Nicke Elife, 2018
Depletion of SIRT6 enzymatic activity increases acute myeloid leukemia cells’ vulnerability to DNA-damaging agents Antonia Cagnetta, Debora Soncini, Stefania Orecchioni, Giovanna Talarico, Paola Minetto, Fabio Guolo, Veronica Retali, Nicoletta Colombo, Enrico Carminati, Marino Clavio, Maurizio Miglino, Micaela Bergamaschi, Aimable Nahimana, Michel Duchosal, Katia Todoerti, Antonino Neri, Mario Passalacqua, Santina Bruzzone, Alessio Nencioni, Francesco Bertolini, Marco Gobbi, Roberto M. Lemoli, Michele Cea Haematologica, 2018
Pharmacological Sirt6 inhibition improves glucose tolerance in a type 2 diabetes mouse model Giovanna Sociali, Mirko Magnone, Silvia Ravera, Patrizia Damonte, Tiziana Vigliarolo, Maria Von Holtey, Valerio G. Vellone, Enrico Millo, Irene Caffa, Michele Cea, Marco Daniele Parenti, Alberto Del Rio, Maximilien Murone, Raul Mostoslavsky, Alessia Grozio, Alessio Nencioni, Santina Bruzzone FASEB Journal, 2017
Abscisic Acid: A Novel Nutraceutical for Glycemic Control Elena Zocchi, Raquel Hontecillas, Andrew Leber, Alexandra Einerhand, Adria Carbo, Santina Bruzzone, Nuria Tubau-Juni, Noah Philipson, Victoria Zoccoli-Rodriguez, Laura Sturla, Josep Bassaganya-Riera Frontiers in Nutrition, 2017
Abscisic acid enhances glucose disposal and induces brown fat activity in adipocytes in vitro and in vivo Laura Sturla, Elena Mannino, Sonia Scarfì, Santina Bruzzone, Mirko Magnone, Giovanna Sociali, Valeria Booz, Lucrezia Guida, Tiziana Vigliarolo, Chiara Fresia, Laura Emionite, Ambra Buschiazzo, Cecilia Marini, Gianmario Sambuceti, Antonio De Flora, Elena Zocchi Biochimica Et Biophysica Acta Molecular and Cell Biology of Lipids, 2017
SIRT6 inhibitors with salicylate-like structure show immunosuppressive and chemosensitizing effects Patrizia Damonte, Giovanna Sociali, Marco Daniele Parenti, Debora Soncini, Inga Bauer, Silvia Boero, Alessia Grozio, Maria von Holtey, Francesco Piacente, Pamela Becherini, Roberta Sanguineti, Annalisa Salis, Gianluca Damonte, Michele Cea, Maximilien Murone, Alessandro Poggi, Alessio Nencioni, Alberto Del Rio, Santina Bruzzone Bioorganic and Medicinal Chemistry, 2017
APO866 increases antitumor activity of cyclosporin - A by inducing mitochondrial and endoplasmic reticulum stress in leukemia cells Antonia Cagnetta, Irene Caffa, Chirag Acharya, Debora Soncini, Prakrati Acharya, Sophia Adamia, Ivana Pierri, Micaela Bergamaschi, Anna Garuti, Giulio Fraternali, Luca Mastracci, Alessandro Provenzani, Chiara Zucal, Gianluca Damonte, Annalisa Salis, Fabrizio Montecucco, Franco Patrone, Alberto Ballestrero, Santina Bruzzone, Marco Gobbi, Alessio Nencioni, Michele Cea Clinical Cancer Research, 2015
Quinazolinedione SIRT6 inhibitors sensitize cancer cells to chemotherapeutics Giovanna Sociali, Lauretta Galeno, Marco Daniele Parenti, Alessia Grozio, Inga Bauer, Mario Passalacqua, Silvia Boero, Alessandra Donadini, Enrico Millo, Marta Bellotti, Laura Sturla, Patrizia Damonte, Alessandra Puddu, Claudia Ferroni, Greta Varchi, Claudio Franceschi, Alberto Ballestrero, Alessandro Poggi, Santina Bruzzone, Alessio Nencioni, Alberto Del Rio European Journal of Medicinal Chemistry, 2015
Discovery of novel and selective SIRT6 inhibitors Marco Daniele Parenti, Alessia Grozio, Inga Bauer, Lauretta Galeno, Patrizia Damonte, Enrico Millo, Giovanna Sociali, Claudio Franceschi, Alberto Ballestrero, Santina Bruzzone, Alberto Del Rio, Alessio Nencioni Journal of Medicinal Chemistry, 2014
Fluridone as a new anti-inflammatory drug Mirko Magnone, Sonia Scarfì, Laura Sturla, Lucrezia Guida, Salvatore Cuzzocrea, Rosanna Di Paola, Santina Bruzzone, Annalisa Salis, Antonio De Flora, Elena Zocchi European Journal of Pharmacology, 2013
Nicotinamide phosphoribosyltransferase inhibition reduces intraplaque CXCL1 production and associated neutrophil infiltration in atherosclerotic mice Rafaela F. da Silva, Rodrigo A. Fraga-Silva, Sabine Steffens, Mathias Fabre, Inga Bauer, Irene Caffa, Mirko Magnone, Giovanna Sociali, Alessandra Quercioli, Graziano Pelli, Sébastien Lenglet, Katia Galan, Fabienne Burger, Sara Vázquez Calvo, Maria Bertolotto, Santina Bruzzone, Alberto Ballestrero, Franco Patrone, Franco Dallegri, Robson A. S. Santos, Nikolaos Stergiopulos, François Mach, Nicolas Vuilleumier, Fabrizio Montecucco, Alessio Nencioni Thrombosis and Haemostasis, 2013
Inhibition of nicotinamide phosphoribosyltransferase reduces neutrophil-mediated injury in myocardial infarction Fabrizio Montecucco, Inga Bauer, Vincent Braunersreuther, Santina Bruzzone, Alexander Akhmedov, Thomas F. Lüscher, Timo Speer, Alessandro Poggi, Elena Mannino, Graziano Pelli, Katia Galan, Maria Bertolotto, Sébastien Lenglet, Anna Garuti, Christophe Montessuit, René Lerch, Corinne Pellieux, Nicolas Vuilleumier, Franco Dallegri, Jacqueline Mage, Carlos Sebastian, Raul Mostoslavsky, Angèle Gayet-Ageron, Franco Patrone, François Mach, Alessio Nencioni Antioxidants and Redox Signaling, 2013
The plant hormone abscisic acid increases in human plasma after hyperglycemia and stimulates glucose consumption by adipocytes and myoblasts Santina Bruzzone, Pietro Ameri, Lucia Briatore, Elena Mannino, Giovanna Basile, Gabriella Andraghetti, Alessia Grozio, Mirko Magnone, Lucrezia Guida, Sonia Scarfì, Annalisa Salis, Gianluca Damonte, Laura Sturla, Alessio Nencioni, Daniela Fenoglio, Francesca Fiory, Claudia Miele, Francesco Beguinot, Vittorio Ruvolo, Mariano Bormioli, Giuseppe Colombo, Davide Maggi, Giovanni Murialdo, Renzo Cordera, Antonio De Flora, Elena Zocchi FASEB Journal, 2012
Binding of abscisic acid to human LANCL2 Laura Sturla, Chiara Fresia, Lucrezia Guida, Alessia Grozio, Tiziana Vigliarolo, Elena Mannino, Enrico Millo, Luca Bagnasco, Santina Bruzzone, Antonio De Flora, Elena Zocchi Biochemical and Biophysical Research Communications, 2011
Synergistic interactions between HDAC and sirtuin inhibitors in human leukemia cells Michele Cea, Debora Soncini, Floriana Fruscione, Lizzia Raffaghello, Anna Garuti, Laura Emionite, Eva Moran, Mirko Magnone, Gabriele Zoppoli, Daniele Reverberi, Irene Caffa, Annalisa Salis, Antonia Cagnetta, Micaela Bergamaschi, Salvatore Casciaro, Ivana Pierri, Gianluca Damonte, Filippo Ansaldi, Marco Gobbi, Vito Pistoia, Alberto Ballestrero, Franco Patrone, Santina Bruzzone, Alessio Nencioni Plos One, 2011
