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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: 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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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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CANDELISE, Niccolo, SCHMITZ, Matthias, THÜNE, Katrin, CRAMM, Maria, RABANO, Alberto, ZAFAR, Saima, STOOPS, Erik, VANDERSTICHELE, Hugo, VILLAR PIQUÉ, Anna, LLORENS TORRES, Franc, ZERR, Inga. Effect of the micro-environment on alpha-synuclein conversion and implication in seeded conversion assays. _Translational Neurodegeneration_. 2020. Vol. 9. [consulta: 23 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/173294]