دورية أكاديمية
Retinoic acid-induced 1 gene haploinsufficiency alters lipid metabolism and causes autophagy defects in Smith-Magenis syndrome
| العنوان: | Retinoic acid-induced 1 gene haploinsufficiency alters lipid metabolism and causes autophagy defects in Smith-Magenis syndrome |
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| المؤلفون: | Turco E. M., Giovenale A. M. G., Sireno L., Mazzoni M., Cammareri A., Marchioretti C., Goracci L., Di Veroli A., Marchesan E., D'Andrea D., Falconieri A., Torres B., Bernardini L., Magnifico M. C., Paone A., Rinaldo S., Della Monica M., D'Arrigo S., Postorivo D., Nardone A. M., Zampino G., Onesimo R., Leoni C., Caicci F., Raimondo D., Binda E., Trobiani L., De Jaco A., Tata A. M., Ferrari D., Cutruzzola F., Mazzoccoli G., Ziviani E., Pennuto M., Vescovi A. L., Rosati J. |
| المساهمون: | Turco, E, Giovenale, A, Sireno, L, Mazzoni, M, Cammareri, A, Marchioretti, C, Goracci, L, Di Veroli, A, Marchesan, E, D'Andrea, D, Falconieri, A, Torres, B, Bernardini, L, Magnifico, M, Paone, A, Rinaldo, S, Della Monica, M, D'Arrigo, S, Postorivo, D, Nardone, A, Zampino, G, Onesimo, R, Leoni, C, Caicci, F, Raimondo, D, Binda, E, Trobiani, L, De Jaco, A, Tata, A, Ferrari, D, Cutruzzola, F, Mazzoccoli, G, Ziviani, E, Pennuto, M, Vescovi, A, Rosati, J |
| بيانات النشر: | Nature Publishing Group GB |
| سنة النشر: | 2022 |
| المجموعة: | Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive) |
| مصطلحات موضوعية: | Autophagy genetic, Haploinsufficiency genetic, Human, Lipid Metabolism genetic, Lipid, Phenotype, Smith-Magenis Syndrome diagnosi, Smith-Magenis Syndrome genetic, Smith-Magenis Syndrome pathology, Trans-Activators metabolism, Transcription Factors metabolism, Tretinoin metabolism, Tretinoin pharmacology |
| 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/36411275; info:eu-repo/semantics/altIdentifier/wos/WOS:000886207500001; volume:13; issue:11; journal:CELL DEATH & DISEASE; https://hdl.handle.net/10281/397819Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85142392229 |
| DOI: | 10.1038/s41419-022-05410-7 |
| الإتاحة: | https://doi.org/10.1038/s41419-022-05410-7Test https://hdl.handle.net/10281/397819Test |
| رقم الانضمام: | edsbas.305D62C4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41419-022-05410-7 |
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