Medicine and Health

Small soluble α-synuclein aggregates are the toxic species in Parkinson's disease

D. Emin, Y. P. Zhang, et al.

Discover the intriguing link between soluble α-synuclein aggregates and neuronal death in Parkinson’s disease, as revealed by groundbreaking research conducted by Derya Emin, Yu P. Zhang, Evgenii Lobanova, and their colleagues. This study uncovers how smaller aggregates induce neuroinflammation, offering critical insights into disease progression.

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Abstract

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

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