Oxidative damage to macromolecules in human Parkinson disease and the rotenone model

Abstract

Parkinson’s disease (PD), the most common neurodegenerative movement disorder, is associated with selective degeneration of nigrostriatal dopamine neurons. While the underlying mechanisms contributing to neurodegeneration in PD appear to be multifactorial, mitochondrial impairment and oxidative stress are widely considered to be central to many forms of the disease. Whether oxidative stress is a cause or consequence of dopaminergic death, there is substantial evidence for oxidative stress in both human PD patients and in animal models of PD, especially using rotenone, a complex I inhibitor. There are many indices of oxidative stress, but this review covers the recent evidence for oxidative damage to nucleic acids, lipids and proteins in both the brain and peripheral tissues in human PD and in the rotenone model. Limitations of the existing literature and future perspectives are discussed. Understanding how each particular macromolecule is damaged by oxidative stress and the interplay of secondary damage to other biomolecules may help design better targets for treatment of PD.

Olive Leaves Extract Improved Sperm Quality and Antioxidant Status in the Testis of Rat Exposed to Rotenone

“…In this context, previous studies showed that ROT could impair antioxidant enzyme activity in the brain of rats and induce Parkinson disease (28,29). Another study reported that ROT by ROS generation induced cell apoptosis (30).…”

“…Exposure to ROT causes enhancement of LPO and antioxidant status impairment in human and animal tissue (28).…”

Succination is Increased on Select Proteins in the Brainstem of the NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) Knockout Mouse, a Model of Leigh Syndrome

“…Increased protein modification by the reactive lipid peroxidation product 4-hydroxy-2-nonenal (HNE) has been described in neurodegenerative diseases (35)(36)(37). Several mitochondrial enzymes, including the pyruvate dehydrogenase, ␣-ketoglutarate dehydrogenase and branched-chain ␣-keto acid dehydrogenase complexes are targets of HNE conjugation (38).…”

Oxidative Stress in Neurodegenerative Diseases

“…Moreover, markers of oxidative damage in PD patients were also detected in the serum and urine [132][133][134][135], but their use as indicators of the course of the disease is far from being useful for clinical practice because the existing data are contradictory [136][137][138]. As has been suggested [136][137][138], these differences may be due to the variability in methods used to measure OS markers.…”