Antioxidants and the Treatment of Neurological Disease

Abstract

A major tenet of modern industrial society is that more is better, that one cannot “get enough of a good thing.” As members of such a society, clinicians and scientists have not been immune to its enculturations and often adopt the “more is better” approach in the pharmacological treatment of human disease. However, anyone who has prescribed drugs to patients in the clinic or applied drugs to cells or animals in the laboratory appreciates that therapy represents a balancing act between the salutary and the toxic effects of the agent utilized. In some cases, the window between these two effects is small and minor increases in dosage can lead to unwanted consequences. Narrow therapeutic windows are particularly apparent under circumstances where the molecular targets of drugs simultaneously play a role in disease pathology and normal cell function. One class of therapeutic agents where this dilemma is becoming more evident is antioxidants. Indeed, recent evidence has begun to define roles for the primary cellular targets of antioxidants, free radicals, not only as mediators of neuronal injury, but also as intracellular second messengers (1–3) that are important in growth factor signaling and vasoregulation as well as human defense against invading micro-organisms (4). Furthermore, some antioxidants become prooxidants under appropriate conditions (5). The question arises: What are the factors one must consider in identifying and developing antioxidants appropriate for use in the clinic? The first part of this chapter will outline one strategy for defining whether an antioxidant is viable as a neuroprotective agent. It will then look toward the future and discuss novel approaches to minimizing free radical toxicity in the nervous system.

Nothing in excess—Solon quoted by Diogenes Laertius in Lives of the Philosophers