Unit:
Κατεύθυνση ΝευροεπιστήμεςLibrary of the School of Science
Author:
Giannopoulou Maria-Ioanna
Supervisors info:
Ξυλούρη Μαρία, Ερευνήτρια Γ', Ίδρυμα Ιατροβιολογικών Ερευνών της Ακαδημίας Αθηνών (ΙΙΒΕΑΑ)
Στεφανής Λεωνίδας, Καθηγητής Νευρολογίας και Νευροβιολογίας, Ιατρική Σχολή
Παπαζαφείρη Παναγιώτα, Αναπληρώτρια Καθηγήτρια Φυσιολογίας Ζώων, Τμήμα Βιολογίας, Σχολή Θετικών Επιστημών
Original Title:
Unraveling the role of TGF-β superfamily signaling in the pathogenesis of a-synucleinopathies
Translated title:
Unraveling the role of TGF-β superfamily signaling in the pathogenesis of a-synucleinopathies
Summary:
Extensive evidence highlights the regulatory role of the transforming growth factor–β (TGF-β) superfamily signaling in the central nervous system. Ligands of this superfamily, including TGF-βs, activins, and bone morphogenetic proteins (BMPs) modulate key events during brain development and brain tissue injury repair, including the regulation of neural patterning, neurogenesis, gliogenesis, microglia development, myelination, and brain wiring. The transcriptional effects of TGF-β signaling are mediated via the Smad protein family members, which, upon binding of components on TGF-β receptors, accumulate in the nucleus to regulate gene expression. Advances in genetics and animal models are indicating an unexpected involvement of the immune system in the initiation and development of neurodegenerative diseases, such as Parkinson’s disease (PD) and multiple system atrophy (MSA) collectively termed as a-synucleinopathies. The key characteristic of both PD and MSA is the abnormal accumulation of the neuronal protein a-Synuclein (aSyn) within neurons or oligodendrocytes, respectively. However, the contribution, of the TGF-β superfamily signalling pathway to disease initiation and progression still remains elusive.
Herein, in order to examine the contribution of the TGF-β pathway on the establishment of aSyn-related pathology, we inoculated rat oligodendroglial cells with human recombinant aSyn pre-formed fibrils (PFFs) or PD patient brain-amplified fibrils and assessed the phosphorylation pattern of TGF-β and BMP Smad-effector proteins. Furthermore, we evaluated the effects of TGF-β receptor I inhibition on the formation of aSyn pathological assemblies within oligodendrocytes. Finally, we performed a preliminary analysis of the activation pattern of the TGF-β and BMP branch and of the neuroinflammatory response in an in vivo model of a-synucleinopathy established by PFF or PD fibril inoculation, utilizing a novel TGF-β/BMP double reporter mouse model.
Main subject category:
Science
Keywords:
animal models, BMP, immune response, multiple system atrophy, oligodendrocytes, Parkinson's disease, Smads, synucleinopathies, TGF-β
File:
File access is restricted until 2026-02-08.
Master Thesis_Giannopoulou.pdf
2 MB
File access is restricted until 2026-02-08.
