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Understanding the role of lysosomes in the intercellular TNT-mediated spreading of α-synuclein and the impact of lysosomal dysfunction

Project description

The role of lysosomes in the intercellular spreading of α-synuclein

The accumulation of misfolded protein aggregates in affected brain regions is a hallmark shared by several neurodegenerative diseases (ND). Misfolded alpha-synuclein (α-syn) accumulates in Parkinson’s disease, and the mechanisms linked to the spreading of α-syn have been implicated in its pathology progression. Recent studies have demonstrated that α-syn fibrils spread between neuronal cells through tunnelling nanotubes (TNTs), thin actin-based membrane protrusions mediating the intercellular transport of various cargoes. These α-syn fibrils induce the aggregation of soluble α-syn in receiving cells. The EU-funded LySyT project will uncover the mechanism by which α-syn fibrils escape from lysosomes to induce the aggregation of monomers in acceptor cells, aiming to understand the correlation between lysosomal storage diseases and NDs.

Call for proposal

H2020-MSCA-IF-2019
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Coordinator

INSTITUT PASTEUR
Address
Rue Du Docteur Roux 25-28
75724 Paris Cedex 15
France
Activity type
Research Organisations
EU contribution
€ 184 707,84