Neurotrophic support and oxidative stress: converging effects in the normal and diseased nervous system.

Oxidative stress and loss of neurotrophic support play major roles in the development of various diseases of the central and peripheral nervous systems. In disorders of the central nervous system such as Alzheimer's, Parkinson's, and Huntington's diseases, oxidative stress appears inextricably linked to the loss of neurotrophic support. A similar situation is seen in the peripheral nervous system in diseases of olfaction, hearing, and vision. Neurotrophic factors act to up-regulate antioxidant enzymes and promote the expression of antioxidant proteins. On the other hand, oxidative stress can cause down-regulation of neurotrophic factors. We propose that normal functioning of the nervous systems involves a positive feedback loop between antioxidant processes and neurotrophic support. Breakdown of this feedback loop in disease states leads to increased oxidative stress and reduced neurotrophic support.