ePoster

ESTABLISHING A CELLULAR AND IN-VIVO MODEL FOR MIMICKING LEWY BODY PATHOLOGY

Shujin Heand 15 co-authors

Charité – Universitätsmedizin

FENS Forum 2026 (2026)
Barcelona, Spain
Board PS04-08PM-250

Presentation

Date TBA

Board: PS04-08PM-250

Poster preview

ESTABLISHING A CELLULAR AND IN-VIVO MODEL FOR MIMICKING LEWY BODY PATHOLOGY poster preview

Event Information

Poster Board

PS04-08PM-250

Abstract

Lewy bodies (LBs) are the histopathological hallmark of Parkinson's disease (PD), with α-synuclein being the major proteinaceous component. The relationship between LB formation and the death of dopaminergic neurons is complex and incompletely understood. It has recently been shown that α-synuclein abnormally aggregates and interacts with other components such as proteins and membranous organelle within neurons. In order to further characterize the formation and pathological role of LBs, we employed the concept of liquid-liquid phase separation to generate a minimal-system where α-synuclein forms aberrant phase separation, which we termed LB-like structures (LBLs). Specifically, by ectopically co-expressing α-synuclein and synphilin-1 in non-neuronal cells, we observed LBLs that exhibited similar physical and biochemical properties to LBs. Specifically, using fluorescence-based microscopy and soft X-ray tomography, we demonstrate the accumulation of membranous organelles, including mitochondria, at the interface of LBLs. In our latest efforts, we were able to recapitulate these findings in-vivo under stressed conditions, using Caenorhabditis elegans as a model. Furthermore, we observed animal mobility dysfunction in the affected worms. Together, our results highlight the value of LBLs as cellular and in-vivo model, potentially enabling the discovery of novel therapeutic strategies, targeting the molecular pathophysiology of PD.

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