Translational Neurodegeneration (Jan 2020)

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

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

DOI
https://doi.org/10.1186/s40035-019-0181-9
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 16

Abstract

Read online

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.

Keywords