Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Dissertation committee:
Παρασκευάς Γεώργιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Καπάκη Ελισσάβετ, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Σκουλάκης Ευθύμιος, Ερευνητής Α΄, Ε.ΚΕ.ΒΕ. Άλ. Φλέμιγκ΄
Βουμβουράκης Κωνσταντίνος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Τσιβγούλης Γεώργιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ευθυμιόπουλος Σπύρος, Καθηγητής, Τμήμα Βιολογίας, ΕΚΠΑ
Κόνσουλας Χρήστος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Τροποποιητές Τ-πρωτεϊνοπαθητικών μηχανισμών
Translated title:
Modifiers of Tauopathy mechanisms
Summary:
Accumulation of highly post-translationally modified Tau proteins is a hallmark of a neurodegenerative disorders known as Tauopathies, the most common of which is Alzheimer’s disease. Although the initiating mechanisms remain largely elusive, pathogenic transformation of physiological Tau isoforms is characterized by their hyper-phosphorylation and eventual aggregate formation. Although hTau phosphorylation and its regulation has received waning attention lately, hyper-phosphorylation at disease linked phosphoepitopes remain strong pathology-linked biomarkers. Therefore, understanding the patterns and regulation of hTau phosphorylation is essential to monitor pathologies and their progression, but just as importantly, to understand its contribution to the IDRmediated structural plasticity of this protein. The results herein describe a sequence of apparent “gatekeeper” phosphorylations, which affect both hTau toxicity and neuronal dysfunction in Drosophila that could also serve as disease biomarkers in patients. The other characteristic linked to neurodegenerative Tauopathies is the insoluble hTau aggregates, that may contribute to toxicity in later stages of the disease. It has been unclear whether cognitive deficits are consequent of aggregate accumulation, compromising generalized neuronal health and eventually leading to neurodegeneration. The data herein, supporting the idea that insoluble aggregates are protective or permissive of neuronal activities that underlie associative learning and memory and aggregation promoting pharmaceuticals may be more appropriate to treat AD-linked cognitive deficits in patients.
Main subject category:
Health Sciences
Keywords:
Tau, Tauopathies, Tau aggregation, Gatekeeper phosphorylation, Drosophila
Number of references:
547
File:
File access is restricted until 2024-07-19.
Vourkou Ergina PhD.pdf
19 MB
File access is restricted until 2024-07-19.
