Neurons with high oxidative metabolism and low antioxidant capacity are particularly vulnerable to oxidative stress in neurodegeneration.
Reactive oxygen species (ROS) accumulate with age and are elevated in AD, PD, HD, and ALS. Neurons are especially vulnerable due to:
- High oxygen consumption
- Post-mitotic state
- Limited regenerative capacity
- Highest oxidative stress in brain
- Lowest glutathione levels
- Iron accumulation
- High metabolic demand
- Calcium influx increases ROS
- ALS models show oxidative damage
- Age-related oxidative damage
- Mitochondrial ROS production
- Limited antioxidant capacity
- Mitochondrial electron transport
- NADPH oxidases
- Peroxisomes
- Glutathione depletion
- SOD/Catalase dysfunction
- Nrf2 pathway impairment
- Lipid peroxidation
- Protein oxidation
- DNA damage (8-OHdG)
- CoQ10
- Vitamin E
- N-acetylcysteine
- Sulforaphane
- Bardoxolone methyl
- Dimethyl fumarate
- Oxidative stress in PD (2022)
- ROS in ALS (2021)