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Your search keyword '"Caterina Veroni"' showing total 5 results
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5 results on '"Caterina Veroni"'

1. The Antioxidant Drug Edaravone Binds to the Aryl Hydrocarbon Receptor (AHR) and Promotes the Downstream Signaling Pathway Activation

Author

Caterina Veroni, Stefania Olla, Maria Stefania Brignone, Chiara Siguri, Alessia Formato, Manuela Marra, Rosa Manzoli, Maria Carla Macario, Elena Ambrosini, Enrico Moro, and Cristina Agresti

Subjects
edaravone, aryl hydrocarbon receptor, oligodendrocyte progenitors, zebrafish, Microbiology, QR1-502
Abstract

A considerable effort has been spent in the past decades to develop targeted therapies for the treatment of demyelinating diseases, such as multiple sclerosis (MS). Among drugs with free radical scavenging activity and oligodendrocyte protecting effects, Edaravone (Radicava) has recently received increasing attention because of being able to enhance remyelination in experimental in vitro and in vivo disease models. While its beneficial effects are greatly supported by experimental evidence, there is a current paucity of information regarding its mechanism of action and main molecular targets. By using high-throughput RNA-seq and biochemical experiments in murine oligodendrocyte progenitors and SH-SY5Y neuroblastoma cells combined with molecular docking and molecular dynamics simulation, we here provide evidence that Edaravone triggers the activation of aryl hydrocarbon receptor (AHR) signaling by eliciting AHR nuclear translocation and the transcriptional-mediated induction of key cytoprotective gene expression. We also show that an Edaravone-dependent AHR signaling transduction occurs in the zebrafish experimental model, associated with a downstream upregulation of the NRF2 signaling pathway. We finally demonstrate that its rapid cytoprotective and antioxidant actions boost increased expression of the promyelinating Olig2 protein as well as of an Olig2:GFP transgene in vivo. We therefore shed light on a still undescribed potential mechanism of action for this drug, providing further support to its therapeutic potential in the context of debilitating demyelinating conditions.

Published
2024
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2. Synthesis and Characterization of Edaravone Analogues as Remyelinating Agents and Putative Mechanistic Probes

Author

Eleonora Colombo, Stefania Olla, Cristina Minnelli, Alessia Formato, Caterina Veroni, Silvia Corbisiero, Mattia Pericolo, Chiara Siguri, Giovanna Mobbili, Cristina Agresti, and Pierfausto Seneci

Subjects
edaravone, amyotrophic lateral sclerosis, prodrugs, mechanism of action, chemical probes, antioxidant activity, Organic chemistry, QD241-441
Abstract

Edaravone (EDA), an antioxidant drug approved for the treatment of ischemic stroke and amyotrophic lateral sclerosis, was recently proposed as a remyelinating candidate for the treatment of multiple sclerosis. Here, we synthesized twelve EDA analogues 2b–4c showing three substitution patterns A–C, searching for improved remyelinating agents and putative molecular targets responsible for their regenerative activity. We profiled them in three primary assays to determine their stimulation of oligodendrocyte progenitor cell metabolism (tetrazolium MTT assay), their antioxidant potential (2,2-diphenyl-1-picrylhydrazyl-DPPH assay) and to predict their bioavailability (virtual ADME profile). Active 4′-carboxylate 2b, 4′-ester 2c and N1-carbamate-4′-ester 4a were further characterized, justifying their in vitro effects and selecting 4a as a putative EDA 1 prodrug suitable for in vivo testing.

Published
2023
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3. A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer's Disease and Mild Cognitive Impairment from Healthy Controls

Author

Paola Piscopo, Valeria Manzini, Roberto Rivabene, Alessio Crestini, Loredana Le Pera, Elisabetta Pizzi, Caterina Veroni, Giuseppina Talarico, Martina Peconi, Anna Elisa Castellano, Carmelo D’Alessio, Giuseppe Bruno, Massimo Corbo, Nicola Vanacore, and Eleonora Lacorte

Subjects
RNA, Untranslated, Organic Chemistry, Pilot Projects, General Medicine, RNA, Circular, Catalysis, Computer Science Applications, Inorganic Chemistry, MicroRNAs, circular RNA, circRNA, Alzheimer Disease, AD, mild cognitive impairment, MCI, biomarkers, microarray Real-Time PCR, Humans, RNA, Cognitive Dysfunction, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Biomarkers
Abstract

The most frequently used biomarkers to support the diagnosis of Alzheimer’s Disease (AD) are Aβ42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyloid deposition. These tests are rather complex and invasive and not easily applicable to clinical practice. Circulating non-coding RNAs, which are inherently stable and easy to manage, have been reported as promising biomarkers for central nervous system conditions. Recently, circular RNAs (circRNAs) as a novel class of ncRNAs have gained attention. We carried out a pilot study on five participants with AD and five healthy controls (HC) investigating circRNAs by Arraystar Human Circular RNA Microarray V2.0. Among them, 26 circRNAs were differentially expressed (FC ≥ 1.5, p < 0.05) in participants with AD compared to HC. From a top 10 of differentially expressed circRNAs, a validation study was carried out on four up-regulated (hsa_circRNA_050263, hsa_circRNA_403959, hsa_circRNA_003022, hsa_circRNA_100837) and two down-regulated (hsa_circRNA_102049, hsa_circRNA_102619) circRNAs in a larger population. Moreover, five subjects with mild cognitive impairment (MCI) were investigated. The analysis confirmed the upregulation of hsa_circRNA_050263, hsa_circRNA_403959, and hsa_circRNA_003022 both in subjects with AD and in MCI compared to HCs. We also investigated all microRNAs potentially interacting with the studied circRNAs. The GO enrichment analysis shows they are involved in the development of the nervous system, and in the cellular response to nerve growth factor stimuli, protein phosphorylation, apoptotic processes, and inflammation pathways, all of which are processes related to the pathology of AD.

Published
2022

4. EBV as the 'gluten of MS' hypothesis: Bypassing autoimmunity

Author

Francesca Aloisi, Caterina Veroni, and Barbara Serafini

Subjects
Celiac Disease, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Multiple Sclerosis, Neurology, Glutens, Humans, Autoimmunity, Neurology (clinical), General Medicine, Antiviral Agents
Abstract

The EBV as the 'gluten of MS' hypothesis discussed by Drosu et al. in a recent Editorial envisages the existence of similar mechanisms leading to celiac disease and multiple sclerosis, such as induction of immunity against an ubiquitous exogenous antigen - gluten and EBV, respectively - and subsequent development of autoimmunity that is maintained by persistence of the initial trigger. While this hypothesis provides the rationale for treating MS with antivirals to lower EBV load, it can be misleading when trying to translate concepts of T cell-B cell interaction and autoimmunity development in celiac disease to multiple sclerosis. Here, we propose that EBV might act as the driver of multiple sclerosis without involving autoimmunity.

Published
2022

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