Title Study of heterotypic droplet formation by alpha-synuclein and prion proteins during liquid-liquid phase separation
Translation of Title Alfa-sinukleino ir priono baltymų heterotipinių lašelių formavimosi tyrimas skysčio–skysčio fazių atsiskyrimo metu.
Authors Miknaitė, Justina
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Pages 66
Keywords [eng] heterotypic LLPS, aggregation, alpha-synuclein, prion protein
Abstract [eng] The formation of protein aggregates and amyloid-like structures in the brain is linked to neu-rodegenerative diseases. Alpha-synuclein and prion protein are two aggregation-prone proteins asso-ciated with Parkinson’s and prion diseases. Recent studies have suggested that cross-interactions between different amyloidogenic proteins and heterotypic liquid-liquid phase separation (LLPS) may contribute to disease progression. In this master’s thesis heterotypic condensate formation and co-aggregation between alpha-synuclein and prion protein was investigated. Recombinant proteins and their fluorescently labelled versions were successfully purified and used to study aggregation kinetics, LLPS and structural changes in near-physiological conditions. The results showed that alpha-synuclein and prion protein co-assemble into heterotypic con-densates in a concentration-dependent fashion. Higher protein concentrations promoted droplet for-mation, increased aggregation, and produced larger clustered assemblies over time. Fluorescence microscopy revealed partitioning of alpha-synuclein into prion protein condensates, whereas prion protein had a bigger influence on alpha-synuclein aggregation and LLPS behavior. FTIR analysis showed that aggregates formed during heterotypic LLPS contain both proteins. Interactions between alpha-synuclein and prion protein induce structural transitions toward more ordered β-sheet-rich ag-gregated structures, indicating the formation of amyloid-like assemblies during co-aggregation. Altogether, this study shows that heterotypic LLPS between alpha-synuclein and prion protein may promote aggregate formation and may be involved in mechanisms related to neurodegenerative disease pathology.
Dissertation Institution Vilniaus universitetas.
Type Master thesis
Language English
Publication date 2026