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2020-01-17

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cc by (c) Candelise et al., 2020
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/173294

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

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https://doi.org/10.1186/s40035-019-0181-9

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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Alfa-sinucleïna, Demència amb cossos de Lewy, Malaltia de Parkinson

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Alpha-synuclein, Lewy body dementia, Parkinson's disease

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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CANDELISE, Niccolo, et al. Effect of the micro-environment on alpha-synuclein conversion and implication in seeded conversion assays. Translational Neurodegeneration. 2020. Vol. 9. [consulted: 14 of August of 2026]. Available at: https://hdl.handle.net/2445/173294

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