Ubiquilin-2 liquid droplets catalyze α-synuclein fibril formation.

ABSTRACT: Liquid-liquid phase separation (LLPS) and subsequent liquid-gel/solid transition are considered common aggregation mechanisms of proteins linked to neurodegenerative diseases. α-synuclein (α-syn), the main factor in Parkinson's disease pathology, has been reported to undergo LLPS, thereby accelerating aggregate formation. However, the precise molecular events involved in the early stages of α-syn aggregation remain controversial. In this study, we show that α-syn aggregation is promoted by droplets formed by ubiquilin-2 (UBQLN2), rather than by α-syn LLPS itself. During the liquid-gel/solid transition of UBQLN2 droplets, α-syn within the droplets transforms into pathogenic fibrils both in vitro and in cells. Immunohistochemistry of brain sections from sporadic Parkinson's disease patients

SUBMITTER: Takei T 

PROVIDER: S-EPMC12623503 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature