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Translational Neurodegeneration
Published in: Translational Neurodegeneration 1/2020

Open Access 01-12-2020 | Parkinson's Disease | Review

Effect of the micro-environment on α-synuclein conversion and implication in seeded conversion assays

Authors: Niccolo Candelise, Matthias Schmitz, Katrin Thüne, Maria Cramm, Alberto Rabano, Saima Zafar, Erik Stoops, Hugo Vanderstichele, Anna Villar-Pique, Franc Llorens, Inga Zerr

Published in: Translational Neurodegeneration | Issue 1/2020

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Abstract

Background

α-Synuclein is a small soluble protein, whose physiological function in the healthy brain is poorly understood. Intracellular inclusions of α-synuclein, referred to as Lewy bodies (LBs), are pathological hallmarks of α-synucleinopathies, such as Parkinson’s disease (PD) or dementia with Lewy bodies (DLB).

Main body

Understanding of the molecular basis as well as the factors or conditions promoting α-synuclein misfolding and aggregation is an important step towards the comprehension of pathological mechanism of α-synucleinopathies and for the development of efficient therapeutic strategies. Based on the conversion and aggregation mechanism of α-synuclein, novel diagnostic tests, such as protein misfolding seeded conversion assays, e.g. the real-time quaking-induced conversion (RT-QuIC), had been developed. In diagnostics, α-synuclein RT-QuIC exhibits a specificity between 82 and 100% while the sensitivity varies between 70 and 100% among different laboratories. In addition, the α-synuclein RT-QuIC can be used to study the α-synuclein-seeding-characteristics of different α-synucleinopathies and to differentiate between DLB and PD.

Conclusion

The variable diagnostic accuracy of current α-synuclein RT-QuIC occurs due to different protocols, cohorts and material etc.. An impact of micro-environmental factors on the α-synuclein aggregation and conversion process and the occurrence and detection of differential misfolded α-synuclein types or strains might underpin the clinical heterogeneity of α-synucleinopathies.
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Metadata
Title
Effect of the micro-environment on α-synuclein conversion and implication in seeded conversion assays
Authors
Niccolo Candelise
Matthias Schmitz
Katrin Thüne
Maria Cramm
Alberto Rabano
Saima Zafar
Erik Stoops
Hugo Vanderstichele
Anna Villar-Pique
Franc Llorens
Inga Zerr
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Translational Neurodegeneration / Issue 1/2020
Electronic ISSN: 2047-9158
DOI
https://doi.org/10.1186/s40035-019-0181-9

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