Figure 1: Pathways leading to oxidative stress in PD and the modulation by PD-related genes. Different pathways contribute to high levels of oxidative stress in dopaminergic neurons, including impaired DA handling (1), mitochondrial dysfunction (2), and neuroinflammation (3). As further discussed in the text, alterations in PD genes can potentiate all these impairments and, therefore, lead to enhanced levels of oxidative stress (see Table 2). UPS dysfunction (4), another important pathogenic pathway in PD, can contribute to the damaging effects of α-syn, due to improper degradation of α-syn mutants or oligomers. Abbreviations: ACO: aconitase, CYT: cytosolic, DA: dopamine, iNOS: inducible nitric oxide synthase, PHOX: NADPH oxidase, UPS: ubiquitin proteasome system, UCP: uncoupling proteins, VESIC: vesicular.