Κατεύθυνση Νευροεπιστήμες
Library of the School of Science

2024-07-31

2024

Bourtouli Nikoleta

Δρ. Βεκρέλλης Κωνσταντίνος, Ερευνητής Α', Ίδρυμα Ιατροβιολογικών Ερευνών της Ακαδημίας Αθηνών, ΙΙΒΕΑΑ

Extracellular Vesicles as Vehicles for Immunotherapy in Neurodegenerative Diseases

English

Extracellular Vesicles as Vehicles for Immunotherapy in Neurodegenerative Diseases

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.

Science

Health Sciences

Immunotherapy; Nanobodies; Extracellular Vesicles; Exosomes; α-synuclein preformed fibrils; protein misfolding; pathology transmission

Yes

3

Yes

81

43

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https://pergamos.lib.uoa.gr/uoa/dl/object/3413121