Soluble α-synuclein aggregates of varying size, structure, and morphology are closely linked to neuronal death in Parkinson’s disease. This study uses a novel size-separation method to demonstrate that aggregates smaller than 200 nm cause significant neuronal death, while larger aggregates are less toxic. Analysis of soluble aggregates from post-mortem human brains reveals similar size and structure to the smaller in vitro aggregates, with Parkinson’s disease brains exhibiting smaller, more inflammatory aggregates than controls. This suggests that small, non-fibrillar α-synuclein aggregates are critical in driving neuroinflammation and disease progression.
Publisher
Nature Communications
Published On
Sep 20, 2022
Authors
Derya Emin, Yu P. Zhang, Evgenii Lobanova, Alyssa Miller, Xuecong Liu, Zengjie Xiao, Helen Dakin, Dimitrios I. Sideris, Jeff Y. L. Lam, Rohan T. Ranasighe, Antonina Kuil, Yanyan Zhao, Suman De, Tuomas P. J. Knowles, Michele Vendruscolo, Francesco S. Ruggeri, Franklin I. Agbiriho, Caroline H. Williams-Gray, David Klenerman
Tags
α-synuclein
Parkinson's disease
neuronal death
neuroinflammation
soluble aggregates
size-separation method
post-mortem analysis
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