Dissertation/ Thesis
Mελέτη παθοφυσιολογικών μηχανισμών σε μοντέλο SLC25A46-επαγόμενης νευρολογικής ασθένειας στο ποντίκι μέσω προσεγγίσεων μοριακής γενετικής και πρωτεομικής ; Studying SLC25A46-mediated pathogenic mechanisms in a genetic mouse model of neuropathology through molecular genetics and proteomics approaches
| العنوان: | Mελέτη παθοφυσιολογικών μηχανισμών σε μοντέλο SLC25A46-επαγόμενης νευρολογικής ασθένειας στο ποντίκι μέσω προσεγγίσεων μοριακής γενετικής και πρωτεομικής ; Studying SLC25A46-mediated pathogenic mechanisms in a genetic mouse model of neuropathology through molecular genetics and proteomics approaches |
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| المؤلفون: | Perivolidi, Vasiliki-Iris, Περιβολίδη, Βασιλική-Ίρις |
| بيانات النشر: | Agricultural University of Athens Γεωπονικό Πανεπιστήμιο Αθηνών |
| سنة النشر: | 2023 |
| المجموعة: | National Archive of PhD Theses (National Documentation Centre Greece) |
| مصطلحات موضوعية: | SLC25A46, Μιτοχόνδριο, Μοντέλο ποντικιού, Πρωτεομική, Νευροεκφυλιστικές ασθένειες, Mitochondrion, Mouse model, Proteomics, Neurodegenerative diseases, Βιολογία, Φυσικές Επιστήμες, Βιοχημεία και Μοριακή βιολογία, Biological Sciences, Natural Sciences, Biochemistry and Molecular Biology |
| الوصف: | Mitochondrial protein SLC25A46, a member of the SLC25 family of mitochondrial carriers, has recently been associated with a wide range of autosomal recessive neurological disorders, including optic atrophy, Charcot-Marie-Tooth type 2, Leigh syndrome, progressive myoclonic ataxia, cerebellar ataxia, and lethal congenital pontocerebellar hypoplasia. Previous studies suggest the involvement of SLC25A46 in mitochondrial dynamics, in the maintenance of the mitochondrial cristae architecture and in mitochondrial communication with the endoplasmic reticulum (ER). However, the pathophysiological role of SLC25A46 remains unknown, making it difficult to understand the pathogenic mechanisms involved. Dr. Douni’s research team using a forward genetics approach, identified a nonsense point mutation in Slc25a46 gene that causes an autosomal recessive neurological phenotype in mouse (Slc25a46atc/atc) with similar clinical symptoms as in patients, including ataxia, episodic crises, unsteady locomotion, muscle weakness, optic atrophy, cerebellar hypoplasia, and delayed development with early lethality. In the present thesis, aiming to further understand the pathophysiological role of SLC25A46 we performed: a) characterization of the skeletal system of Slc25a46atc/atc mice, b) analysis of the mitochondrial activity in Slc25a46atc/atc cerebellum, brain, thymus and spleen in order to detect the effect of SLC25A46-depletion on mitochondrial function, c) identification of the deregulated protein networks and pathways in the cerebellum of Slc25a46atc/atc mice, as well as in an induced SLC25A46-knockdown cell line through proteomic analysis (LC-MS/MS) in order to understand the pathogenic mechanisms involved, d) generation and characterization of the transgenic mice that express SLC25A46-FLAG protein (TgSLC25A46-FLAG), e) identification of in vivo SLC25A46 interactions in mouse tissues of TgSLC25A46-FLAG mice, through immunoprecipitation with anti-FLAG beads and identification of protein complexes containing SLC25A46-FLAG by LC-MS/MS, ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| اللغة: | Greek, Modern (1453-) |
| Relation: | http://hdl.handle.net/10442/hedi/54906 |
| DOI: | 10.12681/eadd/54906 |
| الاتاحة: | http://hdl.handle.net/10442/hedi/54906 https://doi.org/10.12681/eadd/54906 |
| رقم الانضمام: | edsbas.D9E63CDB |
| قاعدة البيانات: | BASE |
| DOI: | 10.12681/eadd/54906 |
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