Long-term spaceflight creates a microgravity environment that may substantially change the kinetics of protein folding and accelerate the progression of neurodegenerative disease pathology. In this project, we study the aggregation behavior of alpha-synuclein—a protein often associated with Parkinson's disease and other synucleinopathies—in the absence of gravity-driven convection currents and the hydrodynamic mixing of molecules. Using a Cell-Free Protein Synthesis (CFPS) system, the SNCA gene will be translated in a microgravity environment on the International Space Station and compared with a 1G Earth control. Prion-like propagation and aggregation kinetics will be assessed using pre-formed alpha-synuclein fibrils. Fibril formation and oligomer stabilization will be quantified by Thioflavin T (ThT) fluorescence assays, ELISA quantification, and Western blot analysis. It is hypothesized that the absence of gravity-driven convection currents and hydrodynamic mixing in microgravity will kinetically trap toxic oligomers and significantly accelerate protein aggregation. The results could improve understanding of risks to astronaut cognitive health and provide insight into molecular mechanisms of neurodegenerative diseases on Earth.
Duressa et al. (Thu,) studied this question.