Neuronal vulnerability in Parkinson’s disease: insights from murine α-synuclein pathology models

) neurons, and parvalbuminergic interneurons, depending on the experimental context. In these models, degeneration is accompanied by mitochondrial and lysosomal dysfunction, calcium dysregulation, presynaptic failure, and neuroinflammatory activation. This review integrates transcriptomic and proteomic data across murine α-synuclein models, revealing differences in selective neuronal vulnerability across models depending on spatiotemporal context and interplay between intrinsic neuronal properties and extrinsic factors. This review paper underscores the need for stage-resolved mapping of vulnerable neuronal and non-neuronal populations in PD and, as well as careful alignment of model selection with the specific mechanistic questions under investigation. It also highlights the need for further single cell and spatiotemporally resolved in vivo studies using reliable molecular markers.