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NEURODEGENERATION

A traffic jam leads to Lewy bodies

Nature Neuroscience volume 22, pages 1043–1045 (2019)Cite this article

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Shahmoradian and colleagues report that the structure of Lewy bodies in Parkinson’s disease consists of α-synuclein and lipid vesicle clusters instead of the long-assumed amyloid fibril core. This finding has implications for our understanding of the underlying pathogenesis of synucleinopathies.

What goes awry when we develop brain diseases? Research into the pathogenesis of neurodegenerative disorders typically focuses on protein misfolding and aggregation. The pathological hallmark of these disorders is focal accumulation of a specific protein—amyloid-β in Alzheimer’s or α-synuclein (α-Syn) aggregation in Parkinson’s disease (PD)—that has a propensity to aggregate and deposit in the brain. For most neurodegenerative diseases, these protein inclusions are thought to consist of amyloid fibrils, rod-like protein structures with a predominantly β-sheet fold. Assembly of these proteins into amyloid fibrils is thought of as the toxic event driving cell death. For PD, structural analyses of its pathological hallmarks, the Lewy body in the soma of a cell and the Lewy neurite along its processes, have revealed a dense accumulation of α-Syn (ref. 1) consisting of amyloid fibrils2. These findings have driven therapeutic and diagnostic research over the last two decades toward studying the α-Syn amyloid formation.

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Fig. 1: Different models of αSyn dysfunction in disease.

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Authors and Affiliations

  1. Dementia Research Institute, University College London, London, United Kingdom

    Tim Bartels

  2. Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA

    Tim Bartels

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  1. Tim Bartels
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Correspondence to Tim Bartels.

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Bartels, T. A traffic jam leads to Lewy bodies. Nat Neurosci 22, 1043–1045 (2019). https://doi.org/10.1038/s41593-019-0435-y

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