Neuroinflammatory contributions play a critical role in Parkinson’s disease onset and progression. Key drivers of neuroinflammation include glial cell reactivity, cytokine signaling, protein aggregation, and mitochondrial dysfunction. Although animal models have been extensively used to investigate the mechanisms, their translational relevance is limited because neuroinflammation in humans is typically chronic, heterogeneous, and sustained over years, whereas in rodents is often acute, transient, and resolves within days to weeks. This paper highlights the utility of human stem cell–derived models in studying Parkinson’s disease by recapitulating patient-specific genetic mutations, neuroinflammatory microglia–neuron interactions, α-synuclein aggregation, and dopaminergic dysfunction, thereby enabling mechanistic studies in the human-relevant models. In addition, we examine how micro- and nanoplastics may exacerbate neuroinflammation in PD. This review concludes by highlighting how human-relevant stem cell-based approaches advance mechanistic understanding of Parkinson’s disease.
Muhammad et al. (2026) studied this question.