Work

The cassette exons of α-synuclein play distinct roles in membrane remodelling and membrane-mediated amyloid formation

Year: 2026

Type: article

Abstract: , or membrane remodelling activity. Despite this, deletions of these residues play a key role in determining the flux through different pathways for lipid-induced amyloid formation, resulting in the formation of structurally distinct fibril populations. Thus, exons 3 and 5 make mechanistically distinct contributions to the relationship between αSyn and membranes with different effects on protein conformation and aggregation. Together, these findings demonstrate that alternative splicing remodels the interplay between αSyn, membranes, and amyloid formation. Mapping the sequence determinants that underlie these processes provides insight into how alternative splicing changes both the physiological functions of αSyn and its involvement in disease.

Source: Chemical Science

DOI: 10.1039/d6sc07425a

Authors: Katherine M. Dewison, Pijush Chakraborty, David J. Brockwell, Sheena E. Radford

Institution: University of Leeds

Language: English

Topic: Parkinson's Disease Mechanisms and Treatments

Subfield: Clinical Neurology

Field: Medicine

Domain: Health Sciences

Open Access status: diamond

Funders: Wellcome Trust, Royal Society, University of Leeds, Medical Research Council

Awards: G1893935450, DTP Bid Led by University of Sheffield, G5989883427, G8807361021