Transcriptional profiling has identified a specific population of dopamine neurons in the substantia nigra that is highly susceptible to degeneration in Parkinson disease (PD). Analysis of nearly 400,000 nuclei from patients with PD and healthy individuals showed that a cell population characterized by expression of AGRT1 was more vulnerable to degeneration than nine other dopamine neuron populations that were identified. Spatially confined to the ventral tier of SNpc, it was highly susceptible to loss in PD and showed the strongest upregulation of targets of TP53 and NR2F2, associated with degeneration. This same vulnerable population was specifically enriched for the heritable risk associated with PD, highlighting the importance of cell-intrinsic processes in determining the differential vulnerability of DA neurons to PD-associated degeneration.

Fyfe I. Vulnerable dopamine neurons identified. Nat Rev Neurol. 2022 Jun 8. doi: 10.1038/s41582-022-00682-1. Epub ahead of print. PMID: 35676370.



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