Simulated microgravity accelerates alpha-synuclein aggregation and induces oxidative stress in an in vitro Parkinson disease model

Abstract

Parkinsons disease (PD) is a neurodegenerative disorder characterized by the accumulation of alpha-synuclein aggregates and progressive neuronal loss in the substantia nigra, with aging being its primary risk factor. The current available models to study PD mechanisms are largely relying on genetic mutations to recapitulate PD typical hallmarks, such as increased alpha-synuclein aggregation. However, they do not model the aging features associated with the disease. Microgravity, a condition experience by astronauts during space missions, is known to induce ageing-like modifications on both systemic and cellular physiology. To replicate the aging-related stress observed in PD patients, we exposed SH-SY5Y and 3K-SNCA mutant cell lines to simulated microgravity. Our findings revealed that simulated microgravity enhanced PD alterations, with a significant increase in misfolded and phosphorylated a-syn. This was accompanied by heightened oxidative stress, as evidenced by increased levels of reactive oxygen species, without a sufficient antioxidant response. These results suggest that simulated microgravity effectively mimics and accelerate the stress associated with aging in PD cell models, regardless of the presence of PD mutation. This study highlights the potential of simulated microgravity as a tool for investigating aging processes in neurodegenerative diseases.