Search

Your search keyword '"Claudia Compagnucci"' showing total 2 results
Start Over Author "Claudia Compagnucci" Publisher nature publishing group
2 results on '"Claudia Compagnucci"'

1. Caspase-dependent apoptosis in Riboflavin Transporter Deficiency iPSCs and derived motor neurons

Author

Chiara Marioli, Maurizio Muzzi, Fiorella Colasuonno, Cristian Fiorucci, Nicolò Cicolani, Stefania Petrini, Enrico Bertini, Marco Tartaglia, Claudia Compagnucci, and Sandra Moreno

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract

Abstract Riboflavin Transporter Deficiency (RTD) is a rare genetic, childhood-onset disease. This pathology has a relevant neurological involvement, being characterized by motor symptoms, ponto-bulbar paralysis and sensorineural deafness. Such clinical presentation is associated with muscle weakness and motor neuron (MN) degeneration, so that RTD is considered part of the MN disease spectrum. Based on previous findings demonstrating energy dysmetabolism and mitochondrial impairment in RTD induced Pluripotent Stem cells (iPSCs) and iPSC-derived MNs, here we address the involvement of intrinsic apoptotic pathways in disease pathogenesis using these patient-specific in vitro models by combined ultrastructural and confocal analyses. We show impaired neuronal survival of RTD iPSCs and MNs. Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) documents severe alterations in patients’ cells, including deranged mitochondrial ultrastructure, and altered plasma membrane and nuclear organization. Occurrence of aberrantly activated apoptosis is confirmed by immunofluorescence and TUNEL assays. Overall, our work provides evidence of a role played by mitochondrial dysfunction in RTD, and identifies neuronal apoptosis as a contributing event in disease pathogenesis, indicating intrinsic apoptosis pathways as possible relevant targets for more effective therapeutical approaches.

Published
2024
Full Text
View/download PDF

2. Genome-wide RNA-seq of iPSC-derived motor neurons indicates selective cytoskeletal perturbation in Brown–Vialetto disease that is partially rescued by riboflavin

Author

Agnese Ramirez, Giacomo P. Comi, Alessia Niceforo, Claudia Compagnucci, Andreina Bordoni, Francesco Fortunato, Stefania Corti, Sabrina Salani, Nereo Bresolin, Enrico Bertini, Valentina Melzi, Federica Rizzo, and Monica Nizzardo

Subjects
0301 basic medicine, Neurofilament, Hearing Loss, Sensorineural, Riboflavin, Bulbar Palsy, Progressive, Induced Pluripotent Stem Cells, Neuronal Outgrowth, Biology, Article, Transcriptome, 03 medical and health sciences, medicine, Autophagy, Humans, Axon, Induced pluripotent stem cell, Cells, Cultured, Cytoskeleton, Regulation of gene expression, Motor Neurons, Multidisciplinary, Gene Expression Profiling, Neurodegeneration, RNA, High-Throughput Nucleotide Sequencing, Cell Differentiation, Motor neuron, medicine.disease, Cell biology, Mitochondria, 030104 developmental biology, medicine.anatomical_structure, Neuroprotective Agents, Biochemistry, Gene Expression Regulation, Dietary Supplements, Energy Metabolism, Genome-Wide Association Study
Abstract

Riboflavin is essential in numerous cellular oxidation/reduction reactions but is not synthesized by mammalian cells. Riboflavin absorption occurs through the human riboflavin transporters RFVT1 and RFVT3 in the intestine and RFVT2 in the brain. Mutations in these genes are causative for the Brown–Vialetto–Van Laere (BVVL), childhood-onset syndrome characterized by a variety of cranial nerve palsies as well as by spinal cord motor neuron (MN) degeneration. Why mutations in RFVTs result in a neural cell–selective disorder is unclear. As a novel tool to gain insights into the pathomechanisms underlying the disease, we generated MNs from induced pluripotent stem cells (iPSCs) derived from BVVL patients as an in vitro disease model. BVVL-MNs explained a reduction in axon elongation, partially improved by riboflavin supplementation. RNA sequencing profiles and protein studies of the cytoskeletal structures showed a perturbation in the neurofilament composition in BVVL-MNs. Furthermore, exploring the autophagy–lysosome pathway, we observed a reduced autophagic/mitophagic flux in patient MNs. These features represent emerging pathogenetic mechanisms in BVVL-associated neurodegeneration, partially rescued by riboflavin supplementation. Our data showed that this therapeutic strategy could have some limits in rescuing all of the disease features, suggesting the need to develop complementary novel therapeutic strategies.

Published
2017

Catalog

Books, media, physical & digital resources
See catalog results