FIGURE 1.

Oxidative stress and its implications in the pathobiologies of neurodegeneration in NDDs and after ischemia or TBI. ROS are produced by multiple sources: endogenously, result from excitotoxic insults, neuroinflammation, ER stress, or mitochondrial dysfunction, whereas exogenously ROS are generated by radiation or xenobiotics. When the production of ROS overwhelms intracellular antioxidant defense, brain cells are exposed to oxidative stress (OS), which may lead to mitochondrial dysfunction and further ROS production. OS impairs the protein degradation system, and thus, hinders the clearance and results in the subsequent deposition of misfolded protein, which in turn, result in lipid peroxidation, protein oxidation, and DNA damage, leading to neuronal death. These events constitute the pathological basis of neurodegenerative diseases (NDDs) and brain aging. OS also contributes to the pathogeneses of secondary damage after cerebral ischemia or other brain injuries. Oxidative metabolites such as the lipid peroxidation products (4-HNE and MDA), protein oxidation products (protein carbonyl moieties), DNA oxidation product (8-OHdG) and antioxidant components such as GSH, bilirubin, uric acid, and antioxidative enzymes (CAT, GPx and SOD) are potential oxidative biomarkers and are elevated in patients with NDDs. OS, oxidative stress; ER, endoplasmic reticulum; NFT, neurofibrillary tangle; AD, Alzheimer’s disease; PD, Parkinson’s disease; GSH, glutathione; GPx, glutathione peroxidase; SOD; superoxide dismutase; CAT, catalase; MDA, malondialdehyde; 8-OHdG, 8-hydroxy-2′-deoxyguanosine, NDD, neurodegenerative disease.