Unit:
Τομέας ΚλινικοεργαστηριακόςLibrary of the School of Health Sciences
Author:
Kalozoumi Georgia
Dissertation committee:
Δέσποινα Σανούδου, Αναπληρώτρια Καθηγήτρια, Ιατρική, ΕΚΠΑ
Αριστείδης Ηλιόπουλος, Καθηγητής, Ιατρική, ΕΚΠΑ
Αντώνιος Τσαρμπόπουλος, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
Χριστίνα Δάλλα, Επίκουρη Καθηγήτρια, Ιατρική, ΕΚΠΑ
Κωνσταντίνος Βεκρέλλης, Ερευνητής Β, ΙΙΒΕΑΑ
Παναγιώτης Πολίτης, Ερευνητής Γ, ΙΙΒΕΑΑ
Antoine Depaulis, Director of Research, INSERM Université Grenoble Alpes
Original Title:
Αναζήτηση νέων θεραπευτικών στόχων για νευροεκφυλιστικές παθήσεις με προσεγγίσεις Γονιδιωματικής
Translated title:
Search for novel therapeutic targets for neurodegenerative diseases via genomic approaches
Summary:
Neurodegenerative diseases are chronic, progressive disorders primarily affecting the Central Nervous System. They represent a serious global healthcare issue, and the majority of currently available treatments are symptomatic or palliative. The Mesio-Temporal Lobe Epilepsy (MTLE) syndrome is an intractable neurodegenerative disease characterized by the recurrence of spontaneous focal seizures in mesial temporal structures of the limbic system of the brain and often associated with hippocampal sclerosis (HS). Clinical management of MTLE is challenging, since it is associated with pharmacoresistance and is the most common type of epilepsy referred for resective surgery.
The aim of this study was to characterize the molecular mechanisms implicated in MTLE pathogenesis and progression, in order to identify novel therapeutic targets for MTLE, through genomic approaches. To achieve this goal, whole genome expression analysis with microarrays was performed on an experimental model that simulates human MTLE, obtained by intrahippocampal kainate (KA) injection in the mouse, at three time points representing distinct stages of MTLE. A multi-level bioinformatical analysis and data mining approach followed, in order to characterize the molecular changes that may affect epileptogenesis and disease progression, and identify central regulatory molecules that may control the observed changes and can serve as candidate therapeutic targets for MTLE. The analysis resulted in the identification of multiple significantly changed genes and molecular pathways at each KA-MTLE stage interrogated, and provided leads for further investigation. Accordingly, additional steps were taken to assess the role of NAPDH oxidase complex in epileptogenesis. Furthermore, global transcriptomic analysis was applied and on hippocampal samples from patients with MTLE-HS, inorder to elucidate the molecular mechanisms associated with this prominent histopathological feature of MTLE. This study provides a comprehensive analysis of hippocampal expression profile during the course of MTLE development and progression, and interrogates novel candidate therapeutic targets for MTLE.
Main subject category:
Health Sciences
Other subject categories:
Health Sciences
Keywords:
Epilepsy, Hippocampus, Transcriptome, Microarrays, RNA
Number of references:
362
