PRKN and Parkinson disease: In this regard, “double-hit or “multi-hit” approaches, in which genetic susceptibility (e.g., LRRK2, parkin or other mutations) is combined with an environmental exposure such as rotenone, MPTP or inflammatory microenvironment may offer a more accurate representation of the complex and heterogeneous pathophysiology of PD (Rudyk and Hayley, 2019; Dwyer et al., 2020).