المؤلفون: Giovenale, Angela Maria Giada, Ruotolo, Giorgia, Soriano, Amata Amy, Turco, Elisa Maria, Rotundo, Giovannina, Casamassa, Alessia, D’Anzi, Angela, Vescovi, Angelo Luigi, Rosati, Jessica

المساهمون: Ministero Della Salute

المصدر: Frontiers in Cell and Developmental Biology ; volume 10 ; ISSN 2296-634X

مصطلحات موضوعية: Cell Biology, Developmental Biology

الوصف: The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is widely expressed in the central and peripheral nervous systems. This receptor is implicated in both brain development and adult neurogenesis thanks to its ability to mediate acetylcholine stimulus (Ach). Copy number variations (CNVs) of CHRNA7 gene have been identified in humans and are genetically linked to cognitive impairments associated with multiple disorders, including schizophrenia, bipolar disorder, epilepsy, Alzheimer’s disease, and others. Currently, α7 receptor analysis has been commonly performed in animal models due to the impossibility of direct investigation of the living human brain. But the use of model systems has shown that there are very large differences between humans and mice when researchers must study the CNVs and, in particular, the CNV of chromosome 15q13.3 where the CHRNA7 gene is present. In fact, human beings present genomic alterations as well as the presence of genes of recent origin that are not present in other model systems as well as they show a very heterogeneous symptomatology that is associated with both their genetic background and the environment where they live. To date, the induced pluripotent stem cells, obtained from patients carrying CNV in CHRNA7 gene, are a good in vitro model for studying the association of the α7 receptor to human diseases. In this review, we will outline the current state of hiPSCs technology applications in neurological diseases caused by CNVs in CHRNA7 gene. Furthermore, we will discuss some weaknesses that emerge from the overall analysis of the published articles.

الإتاحة: https://doi.org/10.3389/fcell.2022.1107881Test

المؤلفون: Giovenale, Angela Maria Giada, Ruotolo, Giorgia, Soriano, Amata Amy, Turco, Elisa Maria, Rotundo, Giovannina, Casamassa, Alessia, D’Anzi, Angela, Vescovi, Angelo Luigi, Rosati, Jessica

المصدر: Frontiers in Cell and Developmental Biology ; volume 11 ; ISSN 2296-634X

مصطلحات موضوعية: Cell Biology, Developmental Biology

الإتاحة: https://doi.org/10.3389/fcell.2023.1141334Test

المؤلفون: Turco, Elisa Maria, Giovenale, Angela Maria Giada, Sireno, Laura, Mazzoni, Martina, Cammareri, Alessandra, Marchioretti, Caterina, Goracci, Laura, Di Veroli, Alessandra, Marchesan, Elena, D'Andrea, Daniel, Falconieri, Antonella, Torres, Barbara, Bernardini, Laura, Magnifico, Maria Chiara, Paone, Alessio, Rinaldo, Serena, Della Monica, Matteo, D'Arrigo, Stefano, Postorivo, Diana, Nardone, Anna Maria, Zampino, Giuseppe, Onesimo, Roberta, Leoni, Chiara, Caicci, Federico, Raimondo, Domenico, Binda, Elena, Trobiani, Laura, De Jaco, Antonella, Tata, Ada Maria, Ferrari, Daniela, Cutruzzolà, Francesca, Mazzoccoli, Gianluigi, Ziviani, Elena, Pennuto, Maria, Vescovi, Angelo Luigi, Rosati, Jessica

المساهمون: Turco, Elisa Maria, Giovenale, Angela Maria Giada, Sireno, Laura, Mazzoni, Martina, Cammareri, Alessandra, Marchioretti, Caterina, Goracci, Laura, Di Veroli, Alessandra, Marchesan, Elena, D'Andrea, Daniel, Falconieri, Antonella, Torres, Barbara, Bernardini, Laura, Magnifico, Maria Chiara, Paone, Alessio, Rinaldo, Serena, Della Monica, Matteo, D'Arrigo, Stefano, Postorivo, Diana, Nardone, Anna Maria, Zampino, Giuseppe, Onesimo, Roberta, Leoni, Chiara, Caicci, Federico, Raimondo, Domenico, Binda, Elena, Trobiani, Laura, De Jaco, Antonella, Tata, Ada Maria, Ferrari, Daniela, Cutruzzolà, Francesca, Mazzoccoli, Gianluigi, Ziviani, Elena, Pennuto, Maria, Vescovi, Angelo Luigi, Rosati, Jessica

مصطلحات موضوعية: Human, Haploinsufficiency, Lipid Metabolism, Transcription Factor, Trans-Activator, Phenotype, Autophagy, Tretinoin, Lipid, Smith-Magenis Syndrome

الوصف: Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder characterized by cognitive and behavioral symptoms, obesity, and sleep disturbance, and no therapy has been developed to alleviate its symptoms or delay disease onset. SMS occurs due to haploinsufficiency of the retinoic acid-induced-1 (RAI1) gene caused by either chromosomal deletion (SMS-del) or RAI1 missense/nonsense mutation. The molecular mechanisms underlying SMS are unknown. Here, we generated and characterized primary cells derived from four SMS patients (two with SMS-del and two carrying RAI1 point mutations) and four control subjects to investigate the pathogenetic processes underlying SMS. By combining transcriptomic and lipidomic analyses, we found altered expression of lipid and lysosomal genes, deregulation of lipid metabolism, accumulation of lipid droplets, and blocked autophagic flux. We also found that SMS cells exhibited increased cell death associated with the mitochondrial pathology and the production of reactive oxygen species. Treatment with N-acetylcysteine reduced cell death and lipid accumulation, which suggests a causative link between metabolic dyshomeostasis and cell viability. Our results highlight the pathological processes in human SMS cells involving lipid metabolism, autophagy defects and mitochondrial dysfunction and suggest new potential therapeutic targets for patient treatment.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36411275; info:eu-repo/semantics/altIdentifier/wos/WOS:000886207500001; volume:13; issue:11; firstpage:981; journal:CELL DEATH & DISEASE; https://hdl.handle.net/11577/3462265Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85142392229

الإتاحة: https://doi.org/10.1038/s41419-022-05410-7Test
https://hdl.handle.net/11577/3462265Test