Article Dans Une Revue Science Advances Année : 2023

α-Synuclein liquid condensates fuel fibrillar αsynuclein growth

α-Synuclein liquid condensates fuel fibrillar α-synuclein growth

Résumé

α-Synuclein (α-Syn) aggregation into fibrils with prion-like features is intimately associated with Lewy pathology and various synucleinopathies. Emerging studies suggest that α-Syn could form liquid condensates through phase separation. The role of these condensates in aggregation and disease remains elusive and the interplay between α-Syn fibrils and α-Syn condensates remains unexplored, possibly due to difficulties in triggering the formation of α-Syn condensates in cells. To address this gap, we developed an assay allowing the controlled assembly/disassembly of α-Syn condensates in cells and studied them upon exposure to preformed α-Syn fibrillar polymorphs. Fibrils triggered the evolution of liquid α-Syn condensates into solid-like structures displaying growing needle-like extensions and exhibiting pathological amyloid hallmarks. No such changes were elicited on α-Syn that did not undergo phase separation. We, therefore, propose a model where α-Syn within condensates fuels exogenous fibrillar seeds growth, thus speeding up the prion-like propagation of pathogenic aggregates.
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Dates et versions

cea-04186084 , version 1 (23-08-2023)

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Leonard Piroska, Alexis Fenyi, Scott Thomas, Marie-Aude Plamont, Virginie Redeker, et al.. α-Synuclein liquid condensates fuel fibrillar αsynuclein growth. Science Advances , 2023, 9 (33), ⟨10.1126/sciadv.adg5663⟩. ⟨cea-04186084⟩
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