A review article on the development of dopaminergic neurons and establishment of dopaminergic neuron–based in vitro models by using immortal cell lines or stem cells to study and treat Parkinson's disease

Abstract The primary pathological hallmark of Parkinson's disease (PD) is the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta, a critical midbrain region. In vitro models based on DA neurons provide a powerful platform for investigating the cellular and molecular mechanisms of PD and testing novel therapeutic strategies. A deep understanding of DA neuron development, including the signalling pathways and transcription factors involved, is essential for advancing PD research. This article first explores the differentiation and maturation processes of DA neurons in the midbrain, detailing the relevant signalling pathways. It then compares various in vitro models, including primary cells, immortalized cell lines, and stem cell‐based models, focusing on the advantages and limitations of each. Special attention is given to the role of immortalized and stem cell models in PD research. This review aims to guide researchers in selecting the most appropriate model for their specific research goals. Ethical considerations and clinical implications of using stem cells in PD research are also discussed.