Oxidative stress and natural antioxidant mechanisms: the role in neurodegeneration. From molecular mechanisms to therapeutic strategies

A lot of evidence exists that oxidative stress is the primary cause of neurodegeneration. Neurons are more susceptible to oxidative damage than other cells due to their high oxygen consumption, low activity of antioxidant enzymes, elevated concentration of polyunsaturated fatty acids in the cell membrane, high number of mitochondria, unfavorable space/volume ratio and vicinity of microglia cells which are likely to produce increased amounts of superoxide radical. Moreover, the tendency to accumulate transition metals in the brain creates a higher probability of Fenton's reaction occurring, a product of which is a hydroxyl radical. Lower activities of natural antioxidants as well as higher concentrations of markers of oxidative damage to proteins, lipids and DNA were observed in patients with neurodegenerative diseases in relation to healthy individuals. There is a lot of research being conducted to develop effective and safe antioxidants that would be useful in the therapy or prevention of neurodegenerative diseases.