This study investigated the effects of simulated Solar Particle Event (SPE) proton radiation on neuron-like SH-SY5Y cells to better understand potential central nervous system risks during long-duration space missions. The primary objective was to optimize an experimental proton irradiation model that reproduces SPE-relevant exposure conditions while generating preliminary biological data on neuronal radiation responses. SH-SY5Y cells were irradiated with 17 MeV protons using the MGC-20E cyclotron at the HUN-REN ATOMKI Accelerator Centre, while SRIM/TRIM Monte Carlo simulations were used to support and refine the experimental setup. During the project, sources of physical and biological variability affecting reproducibility were identified and more reliable irradiation conditions were established. The study's biological analyses showed dose-dependent effects on apoptosis, cell viability, and stress-related gene expression including cFOS transcription, and neuronal markers. Overall, the optimized irradiation model produced measurable biological responses under SPE-like conditions and provides a methodological foundation for future studies of SPE proton radiation effects on neuron-like cells.