This study identifies lactoperoxidase (LPO) as selectively expressed in human substantia nigra dopaminergic neurons, demonstrates LPO can catalyze multiple steps of melanin formation in vitro, and shows transgenic human LPO induces neuromelanin in rat SN, linking LPO activity to neuromelanin…

Pinpointing LPO as a human-specific enzymatic contributor to neuromelanin offers a mechanistic target and biomarker candidate, explains a key species difference in models, and suggests a route to modulate oxidative stress relevant to Parkinson's disease therapy development.

The presence of neuromelanin is a characteristic feature of the human substantia nigra (SN); however, the mechanism of its synthesis and its role in the development of Parkinson's disease remain unclear. Here, we report that the host defense enzyme lactoperoxidase (LPO), which possesses broad antimicrobial activity on mucosal surfaces, is selectively expressed in human dopaminergic neurons, a feature not shared by the rodent SN. We also demonstrate that LPO can catalyze multiple steps of melanin formation in vitro, and transgenic expression of human LPO in the rat SN induces the appearance of neuromelanin. Based on our results, LPO likely contributes to neuromelanin formation in the SN. Since LPO degrades H2O2 during neuromelanin synthesis, the enzyme's activity represents a previously unrecognized link between neuromelanin formation and antioxidant defense mechanisms.