Don’t die like me: Which proteins are responsible for the selective neuronal vulnerability within the substantia nigra?

A hallmark of Parkinson’s disease is the specific degeneration of dopaminergic neurons in the substantia nigra pars compacta. Interestingly, not all of these neurons are equally affected. Studies revealed that neurons located more ventrally within the substantia nigra pars compacta have a higher prevalence to degenerate than those located in the dorsal tier. Reasons for this selective neuronal vulnerability are still unknown. The objective of the present study was to gain a better understanding of molecular differences between these two neuronal subpopulations that can explain the selective neuronal vulnerability within the substantia nigra. For this, both neuronal subpopulations were specifically isolated with laser microdissection. Following, their proteome was analyzed via data independent acquisition mass spectrometry. The results of this study revealed a minor number of proteins that were either specific or differentially expressed in one of the examined neuronal subpopulations within the substantia nigra. These proteins are associated with the cytoskeleton, neuronal plasticity, or calcium homeostasis. With these findings a deeper understanding can be gained of the selective neuronal vulnerability within the substantia nigra and of protective mechanisms against neurodegeneration in specific neuronal subpopulations.