Unfortunately, no definitive therapy for the prevention or cure of AD exists. The currently approved drugs do not target any of the major mechanisms thought to cause the neuronal death/loss seen in AD. Indeed, crucial to the task of preventing or potentially reducing neuronal injury in AD is the ability to elucidate the cellular mechanisms that precipitate neuronal degeneration. As discussed previously, oxidative stress is one of the primary events that occurs in AD pathophysiology. Consequently, antioxidants that prevent the detrimental consequences of oxidative stress are considered to be a promising approach to neuroprotection. Although several epidemiological/clinical studies present controversial results, antioxidants constitute a major part of the panel of clinical and experimental drugs that are currently considered for AD prevention and therapy.
There are various types of antioxidant compounds: direct, indirect, and metabolic. Direct antioxidants have the potential to directly interact with ROS. Their activity is not dependent on endogenous cellular macromole-cules (e.g., enzymes) to exert their primary action but they can by themselves chemically react with the damaging free radicals at the molecular level. Nevertheless, to some extent, there is also interaction with intracellu-lar enzymes since some of these compounds are presumed to be recycled either by endogenous oxireductases directly or indirectly via intracellular reducing shuttles such as ascorbate or some thiols. This class of antioxi-dants include, among others, vitamins, Gingko biloba (flavonoids and terpenoids), and ^-acetylcysteine. Indirect antioxidants are compounds that do not have antioxidant capacity per se but help to prevent/reduce free radicals formation. Among these, we can find metal-chelating agents such as DFO and clioquinol. Metabolic antioxidants are involved in cellular energy production and act as cofactors of several metabolic enzymes. Metabolic antioxidants comprise, among others, idebenone, lipoic acid, and N-acetyl-l-carnitine.
Because this is an extensive topic to discuss, here we present data regarding antioxidants whose therapeutic efficacy have already been analyzed in epidemiological/clinical trials.
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