Κατεύθυνση Ιατρική Γενετική: Κλινική και Εργαστηριακή Κατεύθυνση
Library of the School of Health Sciences

2024-07-18

2024

Kalamata Anastasia

Σοφοκλέους Χρυσταλλένα, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ, Επιβλέπουσα
Κάκουρου Γεωργία, Μοριακή Βιολόγος και Γενετίστρια, Επιστημονικό Προσωπικό, Ιατρική Σχολή, ΕΚΠΑ
Σελέντη Νικολέτα, Βιολόγος, Επιστημονικό Προσωπικό, Ιατρική Σχολή, ΕΚΠΑ

Επανενεργοποίηση χρωμοσώματος Χ ως θεραπευτική προσέγγιση. Το παράδειγμα του συνδρόμου Rett.

Greek

X-chromosome reactivation as a therapeutic approach. The example of Rett syndrome.

X chromosome inactivation (XCI), the random transcriptional silencing of one X chromosome in female mammalian somatic cells, is a mechanism that ensures equal expression of X-linked genes in both sexes. Dose compensation between the sexes results in the inactivation of one X chromosome during development in female mammals. However, X chromosome inactivation is a reversible condition as it can be followed by X chromosome Reactivation (XCR). Rett syndrome (RTT) is an X-linked neurogenetic disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Over two decades of work have established MeCP2 as a protein with crucial roles in the regulation of epigenome, neuronal physiology, synaptic maintenance and behavior. Given the genetic etiology of RTT and the possibility of X chromosome reactivation, significant efforts have been made to design therapeutic approaches to re-express MeCP2.
The aim of this thesis is to review the literature on X chromosome reactivation and its possible implementation in managing X linked manifesting carriers and female patients such as those with Rett syndrome.
For the writing of this thesis, articles were searched in databases. A number of studies have evidence for X-chromosome reactivation, and more specifically for improving the outcome of Rett syndrome patients' phenotype, after reactivation of the MECP2 gene on the inactivated X-chromosome. Numerous studies report that the use of molecules such as decitabine (a DNMT inhibitor that ensures the maintenance of the methylation pattern) and XIST Antisense Oligonucleotides (ASO) lead to reactivation of the X chromosome. However, fully understanding the reactivation phenomenon continues to be a major challenge and it is imperative to design further research studies, as it could be a future therapeutic approach not only for Rett syndrome, but also for other sex-linked diseases.

Health Sciences

X Chromosome Inactivation, Chromatin, XCR, XCI, Rett Syndrome

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https://pergamos.lib.uoa.gr/uoa/dl/object/3410680