Oxidative stress and mitochondrial dysfunction are implicated in the death of dopaminergic neurons in Parkinson's disease (PD). This study used immunohistochemical techniques to detect 4-hydroxy-2-nonenal (HNE)-modified proteins in the substantia nigra (SN) of PD patients and control subjects. HNE is a product of lipid peroxidation and is known to cause cellular damage. The results showed that a significantly higher proportion of nigral neurons in PD patients were positively stained for HNE-modified proteins compared to control subjects. Specifically, 58% of nigral neurons in PD patients were positively stained, while only 9% were in control subjects. This difference was statistically significant. In contrast, oculomotor neurons in the midbrain showed minimal staining in both PD and control subjects, suggesting that oxidative damage is primarily occurring in the SN. The study also found that the medial part of the SN contained the highest proportion of positively stained neurons, which is somewhat unexpected as the lateral part is typically more severely damaged in PD. This discrepancy may be due to the fact that neurons in the lateral part often show severe degenerative changes, including loss of neuromelanin, which could reduce the production of HNE. Additionally, the study found that the proportion of positively stained neurons in the SN was not correlated with age, sex, or duration of levodopa treatment in PD patients, suggesting that oxidative stress is a major factor in the pathogenesis of PD. The findings indicate that oxidative stress is present in the SN of PD patients and may contribute to the death of dopaminergic neurons. The study also highlights the importance of developing drugs to counteract lipid peroxidation in the SN as a potential neuroprotective treatment for PD. The results support the hypothesis that oxidative stress is a key contributor to the pathogenesis of PD and emphasize the need for further research into the mechanisms of oxidative damage in the disease.Oxidative stress and mitochondrial dysfunction are implicated in the death of dopaminergic neurons in Parkinson's disease (PD). This study used immunohistochemical techniques to detect 4-hydroxy-2-nonenal (HNE)-modified proteins in the substantia nigra (SN) of PD patients and control subjects. HNE is a product of lipid peroxidation and is known to cause cellular damage. The results showed that a significantly higher proportion of nigral neurons in PD patients were positively stained for HNE-modified proteins compared to control subjects. Specifically, 58% of nigral neurons in PD patients were positively stained, while only 9% were in control subjects. This difference was statistically significant. In contrast, oculomotor neurons in the midbrain showed minimal staining in both PD and control subjects, suggesting that oxidative damage is primarily occurring in the SN. The study also found that the medial part of the SN contained the highest proportion of positively stained neurons, which is somewhat unexpected as the lateral part is typically more severely damaged in PD. This discrepancy may be due to the fact that neurons in the lateral part often show severe degenerative changes, including loss of neuromelanin, which could reduce the production of HNE. Additionally, the study found that the proportion of positively stained neurons in the SN was not correlated with age, sex, or duration of levodopa treatment in PD patients, suggesting that oxidative stress is a major factor in the pathogenesis of PD. The findings indicate that oxidative stress is present in the SN of PD patients and may contribute to the death of dopaminergic neurons. The study also highlights the importance of developing drugs to counteract lipid peroxidation in the SN as a potential neuroprotective treatment for PD. The results support the hypothesis that oxidative stress is a key contributor to the pathogenesis of PD and emphasize the need for further research into the mechanisms of oxidative damage in the disease.