Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopamine (DA)ergic neurons in the substantia nigra pars compacta and degeneration of projecting nerve fibers in the striatum. Oxidative stress plays a significant role in PD pathogenesis, contributing to cellular dysfunction and cell death. DA metabolism itself can generate reactive oxygen species (ROS), leading to the modification of intracellular macromolecules crucial for cell survival. Mitochondrial dysfunction, which increases ROS production, is another major source of oxidative stress. Additionally, activated microglia release nitric oxide and superoxide during neuroinflammatory responses, exacerbating the oxidative stress. The enzyme NAD(P)H:quinone reductase (NQO1) and other antioxidant enzymes, regulated by the transcription factor Nrf2, are potential therapeutic targets for PD. Current therapies do not delay the neurodegenerative process, highlighting the need for neuroprotective strategies to modify the disease course. Research is ongoing to understand the molecular mechanisms of cell demise in PD and to develop disease-modifying treatments.Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopamine (DA)ergic neurons in the substantia nigra pars compacta and degeneration of projecting nerve fibers in the striatum. Oxidative stress plays a significant role in PD pathogenesis, contributing to cellular dysfunction and cell death. DA metabolism itself can generate reactive oxygen species (ROS), leading to the modification of intracellular macromolecules crucial for cell survival. Mitochondrial dysfunction, which increases ROS production, is another major source of oxidative stress. Additionally, activated microglia release nitric oxide and superoxide during neuroinflammatory responses, exacerbating the oxidative stress. The enzyme NAD(P)H:quinone reductase (NQO1) and other antioxidant enzymes, regulated by the transcription factor Nrf2, are potential therapeutic targets for PD. Current therapies do not delay the neurodegenerative process, highlighting the need for neuroprotective strategies to modify the disease course. Research is ongoing to understand the molecular mechanisms of cell demise in PD and to develop disease-modifying treatments.