Supervisors info:
Δρ. Βεκρέλλης Κωνσταντίνος, Ερευνητής Α', Ίδρυμα Ιατροβιολογικών Ερευνών της Ακαδημίας Αθηνών, ΙΙΒΕΑΑ
Summary:
Synucleinopathies, including Parkinson’s Disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) are characterised by the deposition of a misfolding-prone protein called alpha-synuclein (α-syn). Under these pathologic conditions, misfolded α-syn spreads to healthy neighbouring cells, inducing aggregation of the endogenous protein and thus impairing cellular homeostasis. Immunotherapies aiming to neutralise toxic species of α-syn have been studied for their disease modifying effects. In our study, we developed a passive immunization therapeutic scheme, combining conformation-specific antibodies and nanobodies, targeting oligomeric and fibrillar α-syn forms, and exosomes, a subtype of cup-shaped nanosized extracellular vesicles. Exosomes contain a wide range of micro-molecules and are secreted by all cell types, including brain cells, serving as mediators of inter-cellular communication. In the current study, we have developed a protocol for the generation of brain-derived exosome-antibody/nanobody complexes, as a means to favour the delivery of the conformation-specific agents to aberrant α-syn-bearing target cells. The immunotherapeutic agents were administered in in vitro and in vivo models of PD and their potential to reduce pathology was evaluated.
