Virve Cavallucci

@policlinicogemelli.it

Fondazion Policlinico Universitario A Gemlli IRCCS; Università Cattolica del Sacro Cuore, Istituto di Patologia Generale
Fondazion Policlinico Universitario A Gemlli IRCCS

Virve Cavallucci


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https://researchid.co/virve
33

Scopus Publications

Scopus Publications

  • Vitamin B12 and Reproductive Health: Clinical Insights, Emerging Mechanistic Understanding, and Nutritional Aspects
    Aimee Rachel Mathew, Erisa Selita, Chiara Regano, Claudia Bianco, Veronica Corsetti, Virve Cavallucci, Sandra Moreno, Ada Maria Tata, Marco Fidaleo
    Molecular Reproduction and Development, 2026
    Epidemiological data from assisted reproductive technologies (ART) link vitamin B12 (VitB12) deficiency to shorter gestation, low birth weight, and reduced live birth rates. VitB12 also plays a critical role in fertility for both sexes by supporting gamete quality. Despite some contradictions, emerging evidence suggests early‐life VitB12 deficiency may affect learning and cognitive development. Collectively, these findings suggest that VitB12 is a key determinant of both reproductive and developmental health. Mechanistically, VitB12 acts as a coenzyme in one‐carbon metabolism, and its deficiency leads to elevated homocysteine (Hcy) and methylmalonic acid (MMA) levels, promoting oxidative stress and thereby impairing fertility. Although this remains the most established mechanism, other yet unidentified pathways may also mediate the effects of VitB12 on reproductive function. While the effects of severe VitB12 deficiency are well established, mild deficiencies may develop silently in individuals following plant‐based diets or those with gastrointestinal disorders. Plant‐based sources of VitB12 remain controversial, as many provide only trace amounts or biologically inactive analogs such as pseudovitamin B12, which may interfere with absorption. Further research is needed to evaluate their bioavailability and clinical effectiveness. This review synthesizes clinical evidence, mechanistic insights, and dietary considerations to highlight how VitB12 status shapes reproductive health.
  • Less Is More: A Physiological Dose of Vitamin B12 Enhances Neural Recovery Compared to a High Dose in an H₂O₂-Stressed SH-SY5Y Neural-Like Cell Model
    Aimee Rachel Mathew, Luca Buccini, Anacleto Proietti, Giacomo Di Matteo, Erisa Selita, Ilaria Serangeli, Roberta Stefanelli, Elisa Gazzera, Francesco Mura, Luisa Mannina, Marco Rossi, Antonella De Jaco, Elena Miranda, Ada Maria Tata, Livia Angeloni, Piergiorgio La Rosa, Daniele Passeri, Virve Cavallucci, Marco Fidaleo
    Molecular Neurobiology, 2026
    Vitamin B12 (VitB12) plays a crucial role in neural homeostasis, and a high dose is preferred as treatment to support recovery from neural impairments. However, a significant knowledge gap remains regarding its dose-dependent effects, particularly in its influence on cellular recovery following neural damage. To address this, we utilized retinoic acid-differentiated SH-SY5Y cells, as an in vitro neural model, where we induced neural damage using hydrogen peroxide (H 2 O 2 ), followed by recovery in either a physiological or high dose of VitB12. Our findings reveal that a physiological dose of VitB12 promotes more efficient recovery by enhancing cell survival and promoting neurite elongation after H 2 O 2 insult, compared to a high dose. Recovery with a physiological dose of VitB12 was associated with an early-stage (2 h) activation of antioxidant defenses, suggesting a quicker cellular response to oxidative stress than the high dose. At later stages (24 h), recovery with a physiological dose of VitB12 enhances mitochondrial metabolic activity and morphodynamics, alongside promoting lipid remodeling and increased formation of lipid droplets (LDs). These lipid-related processes may collectively contribute to mitigating oxidative damage and reinforcing cellular resilience during recovery. Overall, our study highlights that a physiological dose of VitB12 not only activates antioxidant defenses earlier than the high dose but also induces later-stage lipid remodeling, potentially supporting neural recovery and homeostasis. Graphical Abstract
  • The Interplay between Liver and Adipose Tissue in the Onset of Liver Diseases: Exploring the Role of Vitamin Deficiency
    Ivan Tattoli, Aimee Rachel Mathew, Antonella Verrienti, Lucia Pallotta, Carola Severi, Fausto Andreola, Virve Cavallucci, Mauro Giorgi, Mara Massimi, Lapo Bencini, Marco Fidaleo
    Cells, 2024
    The deficiency of vitamins, a condition known as “hidden hunger”, causes comprehensive pathological states. Research over the years has identified a relationship between liver diseases and hypovitaminosis or defects in vitamin metabolism. The exact mechanisms remain elusive; however, the crucial involvement of specific vitamins in metabolic functions, alongside the reclassification of liver disease as metabolic dysfunction-associated steatotic liver disease (MASLD), has prompted researchers to investigate the potential cause-effect dynamics between vitamin deficiency and liver disease. Moreover, scientists are increasingly investigating how the deficiency of vitamins might disrupt specific organ crosstalk, potentially contributing to liver disease. Although the concept of a dysmetabolic circuit linking adipose tissue and the liver, leading to liver disease, has been discussed, the possible involvement of vitamin deficiency in this axis is a relatively recent area of study, with numerous critical aspects yet to be fully understood. In this review, we examine research from 2019 to July 2024 focusing on the possible link between liver-adipose tissue crosstalk and vitamin deficiency involved in the onset and progression of non-alcoholic fatty liver disease (NAFLD). Studies report that vitamin deficiency can affect the liver-adipose tissue axis, mainly affecting the regulation of systemic energy balance and inflammation.
  • Vitamin B12 Deficiency and the Nervous System: Beyond Metabolic Decompensation—Comparing Biological Models and Gaining New Insights into Molecular and Cellular Mechanisms
    Aimee Rachel Mathew, Giacomo Di Matteo, Piergiorgio La Rosa, Saviana Antonella Barbati, Luisa Mannina, Sandra Moreno, Ada Maria Tata, Virve Cavallucci, Marco Fidaleo
    International Journal of Molecular Sciences, 2024
    Vitamin B12 (VitB12) is a micronutrient and acts as a cofactor for fundamental biochemical reactions: the synthesis of succinyl-CoA from methylmalonyl-CoA and biotin, and the synthesis of methionine from folic acid and homocysteine. VitB12 deficiency can determine a wide range of diseases, including nervous system impairments. Although clinical evidence shows a direct role of VitB12 in neuronal homeostasis, the molecular mechanisms are yet to be characterized in depth. Earlier investigations focused on exploring the biochemical shifts resulting from a deficiency in the function of VitB12 as a coenzyme, while more recent studies propose a broader mechanism, encompassing changes at the molecular/cellular levels. Here, we explore existing study models employed to investigate the role of VitB12 in the nervous system, including the challenges inherent in replicating deficiency/supplementation in experimental settings. Moreover, we discuss the potential biochemical alterations and ensuing mechanisms that might be modified at the molecular/cellular level (such as epigenetic modifications or changes in lysosomal activity). We also address the role of VitB12 deficiency in initiating processes that contribute to nervous system deterioration, including ROS accumulation, inflammation, and demyelination. Consequently, a complex biological landscape emerges, requiring further investigative efforts to grasp the intricacies involved and identify potential therapeutic targets.
  • Altered vitamin B12 metabolism in the central nervous system is associated with the modification of ribosomal gene expression: new insights from comparative RNA dataset analysis
    Aimee Rachel Mathew, Virve Cavallucci, Marco Fidaleo
    Functional and Integrative Genomics, 2023
    Recent studies have confirmed the direct role of vitamin B12 (VitB12) in the central nervous system (CNS) homeostasis; nevertheless, the detailed mechanisms are poorly understood. By analyzing RNA-Seq and microarray datasets obtained from databanks, this study aims to identify possible basic mechanisms, related to the brain, involved in altering the gene expression under VitB12 deficiency mimicking conditions. The database inquiry returned datasets generated from distinctly heterogeneous experimental sets and considering the quality and relevance requirements, two datasets from mouse and one from rat models were selected. The analyses of individual datasets highlighted a change in ribosomal gene expression in VitB12 deficiency mimicking conditions within each system. Specifically, a divergent regulation was observed depending on the animal model: mice showed a down regulation of the ribosomal gene expression, while rats an upregulation. Interestingly, E2f1 was significantly upregulated under VitB12 deficiency mimicking conditions in the animal models, with a greater upregulation in rats. The rat model also revealed putative E2F1 Transcription Factor Binding Sites (TFBSs) in the promoter of the differently regulated genes involved in ribosomal gene expression. This suggested the possibility that E2F1, being greater expressed in rats, could activate the ribosomal genes having E2F1 TFBSs, thus giving a plausible explication to the divergent regulation observed in animal models. Despite the great diversity of the experimental sets used to generate the datasets considered, a common alteration of the ribosomes exists, thereby indicating a possible basic and conserved response to VitB12 deficiency. Moreover, these findings could provide new insights on E2F1 and its association with CNS homeostasis and VitB12 deficiency. Graphical Abstract
  • Proinflammatory and Cancer-Promoting Pathobiont Fusobacterium nucleatum Directly Targets Colorectal Cancer Stem Cells
    Virve Cavallucci, Ivana Palucci, Marco Fidaleo, Antonella Mercuri, Letizia Masi, Valeria Emoli, Giada Bianchetti, Micol Eleonora Fiori, Gilad Bachrach, Franco Scaldaferri, Giuseppe Maulucci, Giovanni Delogu, Giovambattista Pani
    Biomolecules, 2022
    Intestinal bacterial communities participate in gut homeostasis and are recognized as crucial in bowel inflammation and colorectal cancer (CRC). Fusobacterium nucleatum (Fn), a pathobiont of the oral microflora, has recently emerged as a CRC-associated microbe linked to disease progression, metastasis, and a poor clinical outcome; however, the primary cellular and/or microenvironmental targets of this agent remain elusive. We report here that Fn directly targets putative colorectal cancer stem cells (CR-CSCs), a tumor cell subset endowed with cancer re-initiating capacity after surgery and chemotherapy. A patient-derived CSC line, highly enriched (70%) for the stem marker CD133, was expanded as tumor spheroids, dissociated, and exposed in vitro to varying amounts (range 100–500 MOI) of Fn. We found that Fn stably adheres to CSCs, likely by multiple interactions involving the tumor-associated Gal-GalNac disaccharide and the Fn-docking protein CEA-family cell adhesion molecule 1 (CEACAM-1), robustly expressed on CSCs. Importantly, Fn elicited innate immune responses in CSCs and triggered a growth factor-like, protein tyrosine phosphorylation cascade largely dependent on CEACAM-1 and culminating in the activation of p42/44 MAP kinase. Thus, the direct stimulation of CSCs by Fn may contribute to microbiota-driven colorectal carcinogenesis and represent a target for innovative therapies.
  • The Influence of Gut Microbiota on Neurogenesis: Evidence and Hopes
    Fiorella Sarubbo, Virve Cavallucci, Giovambattista Pani
    Cells, 2022
    Adult neurogenesis (i.e., the life-long generation of new neurons from undifferentiated neuronal precursors in the adult brain) may contribute to brain repair after damage, and participates in plasticity-related processes including memory, cognition, mood and sensory functions. Among the many intrinsic (oxidative stress, inflammation, and ageing), and extrinsic (environmental pollution, lifestyle, and diet) factors deemed to impact neurogenesis, significant attention has been recently attracted by the myriad of saprophytic microorganismal communities inhabiting the intestinal ecosystem and collectively referred to as the gut microbiota. A growing body of evidence, mainly from animal studies, reveal the influence of microbiota and its disease-associated imbalances on neural stem cell proliferative and differentiative activities in brain neurogenic niches. On the other hand, the long-claimed pro-neurogenic activity of natural dietary compounds endowed with antioxidants and anti-inflammatory properties (such as polyphenols, polyunsaturated fatty acids, or pro/prebiotics) may be mediated, at least in part, by their action on the intestinal microflora. The purpose of this review is to summarise the available information regarding the influence of the gut microbiota on neurogenesis, analyse the possible underlying mechanisms, and discuss the potential implications of this emerging knowledge for the fight against neurodegeneration and brain ageing.
  • The leucine catabolite and dietary supplement β-hydroxy-β-methyl butyrate (Hmb) as an epigenetic regulator in muscle progenitor cells
    Virve Cavallucci, Giovambattista Pani
    Metabolites, 2021
    β-Hydroxy-β-Methyl Butyrate (HMB) is a natural catabolite of leucine deemed to play a role in amino acid signaling and the maintenance of lean muscle mass. Accordingly, HMB is used as a dietary supplement by sportsmen and has shown some clinical effectiveness in preventing muscle wasting in cancer and chronic lung disease, as well as in age-dependent sarcopenia. However, the molecular cascades underlying these beneficial effects are largely unknown. HMB bears a significant structural similarity with Butyrate and β-Hydroxybutyrate (βHB), two compounds recognized for important epigenetic and histone-marking activities in multiple cell types including muscle cells. We asked whether similar chromatin-modifying actions could be assigned to HMB as well. Exposure of murine C2C12 myoblasts to millimolar concentrations of HMB led to an increase in global histone acetylation, as monitored by anti-acetylated lysine immunoblotting, while preventing myotube differentiation. In these effects, HMB resembled, although with less potency, the histone deacetylase (HDAC) inhibitor Sodium Butyrate. However, initial studies did not confirm a direct inhibitory effect of HMB on HDACs in vitro. β-Hydroxybutyrate, a ketone body produced by the liver during starvation or intense exercise, has a modest effect on histone acetylation of C2C12 cells or in vitro HDAC inhibitor activities, and, unlike Butyrate and HMB, did not interfere with myotube formation in a myoblast differentiation assay. Instead, βHB dramatically increased lysine β-hydroxybutyrylation (Kbhb) of histone tails, an epigenetic mark associated with fasting responses and muscle catabolic states. However, when C2C12 cells were exposed to βHB in the presence of equimolar HMB this chromatin modification was drastically reduced, pointing to a role for HMB in attenuating ketosis-associated muscle wasting. In conclusion, while their mechanistic underpinnings remain to be clarified, these preliminary observations highlight novel and potentially important activities of HMB as an epigenetic regulator and βHB antagonist in muscle precursor cells, to be further explored in their biomedical implications.
  • Nutrients and neurogenesis: the emerging role of autophagy and gut microbiota
    Virve Cavallucci, Marco Fidaleo, Giovambattista Pani
    Current Opinion in Pharmacology, 2020
    Adult neurogenesis, the generation of mature functional neurons from neural stem cells in specific regions of the adult mammalian brain, is implicated in brain physiology, neurodegeneration and mood disorders. Among the many intrinsic and extrinsic factors that modulate neurogenic activity, the role of nutrients, energy metabolism, and gut microbiota has recently emerged. It is increasingly evident that excessive calorie intake accelerates the age-dependent decline of neurogenesis, while calorie restriction and physical exercise have the opposite effect. Mechanistically, nutrient availability could affect neurogenesis by modulating autophagy, a cell-rejuvenating process, in neural stem cells. In parallel, diet can alter the composition of gut microbiota thus impacting the intestine-neurogenic niche communication. These exciting breakthroughs are here concisely reviewed.
  • Nutrients, neurogenesis and brain ageing: From disease mechanisms to therapeutic opportunities
    Marco Fidaleo, Virve Cavallucci, Giovambattista Pani
    Biochemical Pharmacology, 2017
    Appreciation of the physiological relevance of mammalian adult neurogenesis has in recent years rapidly expanded from a phenomenon of homeostatic cell replacement and brain repair to the current view of a complex process involved in high order cognitive functions. In parallel, an array of endogenous or exogenous triggers of neurogenesis has also been identified, among which metabolic and nutritional cues have drawn significant attention. Converging evidence from animal and in vitro studies points to nutrient sensing and energy metabolism as major physiological determinants of neural stem cell fate, and modulators of the whole neurogenic process. While the cellular and molecular circuitries underlying metabolic regulation of neurogenesis are still incompletely understood, the key role of mitochondrial activity and dynamics, and the importance of autophagy have begun to be fully appreciated; moreover, nutrient‐sensitive pathways and transducers such as the insulin‐IGF cascade, the AMPK/mTOR axis and the transcription regulators CREB and Sirt‐1 have been included, beside more established “developmental” signals like Notch and Wnt, in the molecular networks that dictate neural‐stem‐cell self‐renewal, migration and differentiation in response to local and systemic inputs. Many of these nutrient‐related cascades are deregulated in the contest of metabolic diseases and in ageing, and may contribute to impaired neurogenesis and thus to cognition defects observed in these conditions. Importantly, accumulating knowledge on the metabolic control of neurogenesis provides a theoretical framework for the trial of new or repurposed drugs capable of interfering with nutrient sensing as enhancers of neurogenesis in the context of neurodegeneration and brain senescence.
  • Autophagy Inhibition Favors Survival of Rubrospinal Neurons After Spinal Cord Hemisection
    Elisa Bisicchia, Laura Latini, Virve Cavallucci, Valeria Sasso, Vanessa Nicolin, Marco Molinari, Marcello D’Amelio, Maria Teresa Viscomi
    Molecular Neurobiology, 2017
  • Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer's disease
    Annalisa Nobili, Emanuele Claudio Latagliata, Maria Teresa Viscomi, Virve Cavallucci, Debora Cutuli, Giacomo Giacovazzo, Paraskevi Krashia, Francesca Romana Rizzo, Ramona Marino, Mauro Federici, Paola De Bartolo, Daniela Aversa, Maria Concetta Dell’Acqua, Alberto Cordella, Marco Sancandi, Flavio Keller, Laura Petrosini, Stefano Puglisi-Allegra, Nicola Biagio Mercuri, Roberto Coccurello, Nicola Berretta, Marcello D’Amelio
    Nature Communications, 2017
  • Autophagy Mechanisms for Brain Recovery. Keep It Clean, Keep It Alive
    Maria Teresa Viscomi, Marcello D’Amelio, Annalisa Nobili, Virve Cavallucci, Laura Latini, Elisa Bisicchia, Valeria Sasso, Marco Molinari
    Contemporary Clinical Neuroscience, 2017
  • Epilepsy, amyloid-β, and D1 dopamine receptors: a possible pathogenetic link?
    Cinzia Costa, Lucilla Parnetti, Marcello D'Amelio, Alessandro Tozzi, Michela Tantucci, Andrea Romigi, Sabrina Siliquini, Virve Cavallucci, Massimiliano Di Filippo, Petra Mazzocchetti, Claudio Liguori, Annalisa Nobili, Paolo Eusebi, Nicola B. Mercuri, Paolo Calabresi
    Neurobiology of Aging, 2016
  • Neural Stem Cells and Nutrients: Poised Between Quiescence and Exhaustion
    Virve Cavallucci, Marco Fidaleo, Giovambattista Pani
    Trends in Endocrinology and Metabolism, 2016
  • Effects of Anti-NMDA Antibodies on Functional Recovery and Synaptic Rearrangement Following Hemicerebellectomy
    Daniela Laricchiuta, Virve Cavallucci, Debora Cutuli, Paola De Bartolo, Paola Caporali, Francesca Foti, Carsten Finke, Marcello D’Amelio, Mario Manto, Laura Petrosini
    Neuromolecular Medicine, 2016
  • Neuregulin 1 signalling modulates mGluR1 function in mesencephalic dopaminergic neurons
    A Ledonne, A Nobili, E C Latagliata, V Cavallucci, E Guatteo, S Puglisi-Allegra, M D'Amelio, N B Mercuri
    Molecular Psychiatry, 2015
  • Acute focal brain damage alters mitochondrial dynamics and autophagy in axotomized neurons
    V Cavallucci, E Bisicchia, M T Cencioni, A Ferri, L Latini, A Nobili, F Biamonte, F Nazio, F Fanelli, S Moreno, M Molinari, M T Viscomi, M D'Amelio
    Cell Death and Disease, 2014
  • Cannabinoid CB2 receptor (CB2R) stimulation delays rubrospinal mitochondrial-dependent degeneration and improves functional recovery after spinal cord hemisection by ERK1/2 inactivation
    L Latini, E Bisicchia, V Sasso, V Chiurchiù, V Cavallucci, M Molinari, M Maccarrone, M T Viscomi
    Cell Death and Disease, 2014
  • Key role of mitochondria in Alzheimer's disease synaptic dysfunction
    Virve Cavallucci, Caterina Ferraina, Marcello D'Amelio
    Current Pharmaceutical Design, 2013
  • Calcineurin inhibition rescues early synaptic plasticity deficits in a mouse model of Alzheimer's disease
    Virve Cavallucci, Nicola Berretta, Annalisa Nobili, Robert Nisticò, Nicola B. Mercuri, Marcello D’Amelio
    Neuromolecular Medicine, 2013
  • A New Transgenic Mouse Model for Studying the Neurotoxicity of Spermine Oxidase Dosage in the Response to Excitotoxic Injury
    Manuela Cervelli, Gabriella Bellavia, Marcello D'Amelio, Virve Cavallucci, Sandra Moreno, Joachim Berger, Roberta Nardacci, Manuela Marcoli, Guido Maura, Mauro Piacentini, Roberto Amendola, Francesco Cecconi, Paolo Mariottini
    Plos One, 2013
  • CREB is necessary for synaptic maintenance and learning-induced changes of the ampa receptor GluA1 subunit
    Silvia Middei, Gry Houeland, Virve Cavallucci, Martine Ammassari-Teule, Marcello D'Amelio, Hélène Marie
    Hippocampus, 2013
  • Emerging role of mitochondria dysfunction in the onset of neurodegenerative diseases
    Journal of Biological Regulators and Homeostatic Agents, 2013
  • Aβ toxicity in Alzheimer's disease
    Virve Cavallucci, Marcello D’Amelio, Francesco Cecconi
    Molecular Neurobiology, 2012
  • Insulin receptor β-subunit haploinsufficiency impairs hippocampal late-phase ltp and recognition memory
    Robert Nisticò, Virve Cavallucci, Sonia Piccinin, Simone Macrì, Marco Pignatelli, Bisan Mehdawy, Fabio Blandini, Giovanni Laviola, Davide Lauro, Nicola B. Mercuri, Marcello D’Amelio
    Neuromolecular Medicine, 2012
  • Stimulation of autophagy by rapamycin protects neurons from remote degeneration after acute focal brain damage
    Maria Teresa Viscomi, Marcello D’Amelio, Virve Cavallucci, Laura Latini, Elisa Bisicchia, Francesca Nazio, Francesca Fanelli, Mauro Maccarrone, Sandra Moreno, Francesco Cecconi, Marco Molinari
    Autophagy, 2012
  • Matter of life and death: The pharmacological approaches targeting apoptosis in brain diseases
    Virve Cavallucci, Marcello D'Amelio
    Current Pharmaceutical Design, 2011
  • Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer's disease
    Marcello D'Amelio, Virve Cavallucci, Silvia Middei, Cristina Marchetti, Simone Pacioni, Alberto Ferri, Adamo Diamantini, Daniela De Zio, Paolo Carrara, Luca Battistini, Sandra Moreno, Alberto Bacci, Martine Ammassari-Teule, Hélène Marie, Francesco Cecconi
    Nature Neuroscience, 2011
  • Neuronal caspase-3 signaling: Not only cell death
    M D'Amelio, V Cavallucci, F Cecconi
    Cell Death and Differentiation, 2010
  • Physiological and pathological role of apoptosis
    Virve Cavallucci, Marcello D’Amelio
    Apoptosome an Up and Coming Therapeutical Tool, 2010
  • Inflammation triggers synaptic alteration and degeneration in experimental autoimmune encephalomyelitis
    D. Centonze, L. Muzio, S. Rossi, F. Cavasinni, V. De Chiara, A. Bergami, A. Musella, M. D'Amelio, V. Cavallucci, A. Martorana, A. Bergamaschi, M. T. Cencioni, A. Diamantini, E. Butti, G. Comi, G. Bernardi, F. Cecconi, L. Battistini, R. Furlan, G. Martino
    Journal of Neuroscience, 2009
  • Chapter 15 Analysis of Neuronal Cell Death in Mammals
    Marcello D'Amelio, Virve Cavallucci, Adamo Diamantini, Francesco Cecconi
    Methods in Enzymology, 2008