The aim of this study was twofold: (i) to develop potential natural inhibitor hits for multiple protein targets (NMDA, LRRK2, TrkA) related to neurodegenerative diseases (AD, PD), and (ii) to demonstrate the usefulness of a hybrid approach comprising QSAR (machine learning: ANN, MLR, virtual screening) and molecular modeling (molecular docking and molecular dynamics) as applied to the natural compound space. This evidence concerns the gene NTRK1 and Parkinson disease.