Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopamine (DA) neurons in the substantia nigra and degeneration of projecting fibers in the striatum. Oxidative stress is a major contributor to the disease, arising from DA metabolism, mitochondrial dysfunction, and neuroinflammation. DA metabolism generates reactive oxygen species (ROS), leading to oxidative damage of cellular components, including proteins and DNA. Mitochondrial dysfunction increases ROS production, further exacerbating oxidative stress. Neuroinflammation, driven by activated microglia, releases nitric oxide and superoxide, which contribute to oxidative stress and neuronal damage. Damaged DAergic neurons release molecules like α-synuclein, neuromelanin, and matrix metalloproteinase-3 (MMP-3), which further promote neuroinflammation and oxidative stress. DA quinone, a byproduct of DA oxidation, covalently modifies proteins such as α-synuclein, parkin, DJ-1, and UCH-L1, leading to their dysfunction and contributing to neuronal death. DA quinone also causes mitochondrial dysfunction and disrupts protein folding processes. Neuromelanin, a product of DA oxidation, can exacerbate neuroinflammation and neurodegeneration. MMP-3, upregulated by oxidative stress, activates microglia, leading to the release of reactive nitrogen species and cytokines, which further drive neuroinflammation and neuronal damage. Therapeutic strategies targeting oxidative stress, such as NAD(P)H:quinone reductase (NQO1), which is regulated by the transcription factor Nrf2, offer potential neuroprotective approaches. NQO1 helps reduce oxidative stress by detoxifying quinones and maintaining antioxidant molecules like α-tocopherol and coenzyme Q10. Induction of NQO1 through Nrf2 activation may provide a disease-modifying therapy for PD. Current research focuses on understanding the molecular mechanisms of PD pathogenesis to develop effective treatments. Despite advances, no therapy has yet been found to delay the neurodegenerative process, highlighting the need for further research into oxidative stress and neuroinflammation as key targets for PD treatment.Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopamine (DA) neurons in the substantia nigra and degeneration of projecting fibers in the striatum. Oxidative stress is a major contributor to the disease, arising from DA metabolism, mitochondrial dysfunction, and neuroinflammation. DA metabolism generates reactive oxygen species (ROS), leading to oxidative damage of cellular components, including proteins and DNA. Mitochondrial dysfunction increases ROS production, further exacerbating oxidative stress. Neuroinflammation, driven by activated microglia, releases nitric oxide and superoxide, which contribute to oxidative stress and neuronal damage. Damaged DAergic neurons release molecules like α-synuclein, neuromelanin, and matrix metalloproteinase-3 (MMP-3), which further promote neuroinflammation and oxidative stress. DA quinone, a byproduct of DA oxidation, covalently modifies proteins such as α-synuclein, parkin, DJ-1, and UCH-L1, leading to their dysfunction and contributing to neuronal death. DA quinone also causes mitochondrial dysfunction and disrupts protein folding processes. Neuromelanin, a product of DA oxidation, can exacerbate neuroinflammation and neurodegeneration. MMP-3, upregulated by oxidative stress, activates microglia, leading to the release of reactive nitrogen species and cytokines, which further drive neuroinflammation and neuronal damage. Therapeutic strategies targeting oxidative stress, such as NAD(P)H:quinone reductase (NQO1), which is regulated by the transcription factor Nrf2, offer potential neuroprotective approaches. NQO1 helps reduce oxidative stress by detoxifying quinones and maintaining antioxidant molecules like α-tocopherol and coenzyme Q10. Induction of NQO1 through Nrf2 activation may provide a disease-modifying therapy for PD. Current research focuses on understanding the molecular mechanisms of PD pathogenesis to develop effective treatments. Despite advances, no therapy has yet been found to delay the neurodegenerative process, highlighting the need for further research into oxidative stress and neuroinflammation as key targets for PD treatment.