Specialty Molecular Biomedicine Mechanisms of Disease, Molecular and Cellular Therapies, and Bioinnovation
Library of the School of Health Sciences

2020-10-14

2020

Tsafaras Georgios

Κωνσταντίνος Βεκρέλλης, Ερευνητής Γ΄, Ίδρυμα Ιατροβιολογικών Ερευνών Ακαδημίας Αθηνών
Λεωνίδας Στεφανής, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ευαγγελία Εμμανουηλίδου, Επίκουρος Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ

Exosomes as vehicles for immunotherapy in neurodegenerative diseases

English

Exosomes as vehicles for immunotherapy in neurodegenerative diseases

Parkinson’s disease (PD) is a multi-system neurodegenerative disorder characterized by the progressive loss, of the dopaminergic neurons residing in the substantia Nigra pars compacta. The major pathological feature of the disease is the accumulation of large proteinaceous inclusions, either in the neuronal cell bodies or in the degenerating terminals, termed ‘Lewy Bodies’ (LB) or ‘Lewy neurites’ (LN), respectively. The main structural component of these aggregates is alpha-synuclein (α-syn), a small pre-synaptic protein, genetically and biochemically linked to PD pathophysiology, highly prone to misfolding.
In PD as well as in other synucleinopathies, a-syn increased levels, aggregation and secretion in the extracellular space are the main culprits for cell-to-cell transmission of the pathology, via seeding of the endogenous α-syn protein. Importantly, a-syn is delivered to the extracellular milieu, partly through its association with exosomes; these are nano-sized cup-like externalized vehicles that play a major role in inter-cellular communication, via carrying and delivering their molecular/biochemical cargo.
Our study aims to take advantage of the unique biophysical and biochemical properties of exosomes as well as their ability to interact with a-syn, engineering them in such a way as to carry antibodies targeting misfolded a-syn. In particular, we isolate mouse brain derived exosomes and incubate them with the anti-fibrillar a-syn antibody SynO2, under various conditions. The integrity of exosomes is verified by electron microscopy, whereas the sufficient binding of the antibody is confirmed by western-blot analysis. Exosome-bound antibodies are further applied in vitro, and their uptake by recipient cells as well their capacity to alleviate α-syn burden are monitored. The ultimate goal is to optimize this approach for in vivo use in order to validate its potential as a therapeutic tool. Such a strategy can be applied not only in PD and related synucleinopathies but also for other misfolded protein diseases.

Health Sciences

Exosomes, Immunotherapy, a-synuclein

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https://pergamos.lib.uoa.gr/uoa/dl/object/2924732