Alzheimer's disease and antioxidant therapy: how long how far?

Alzheimer's disease (AD) has become a health problem to societies worldwide affecting millions of people. AD normally ensues in middle and late life but its specific cause remains unknown. Besides amyloid-β deposition and hyperphosphorylated tau protein, increased production of reactive species (RS) has also been described to be a hallmark in early steps of this disorder. Antioxidant therapy has received considerable attention over the last years as a promising approach to delay or slow the neurodegeneration progression in AD either by boosting the pool of endogenous antioxidants (e.g.vitamins, coenzyme Q10 or melatonin) or by the intake of dietary antioxidants, such as phenolic compounds of flavonoid or non-flavonoid type. However, the majority of antioxidants studied so far have limited success in clinical trials, a fact that could be related to their poor distribution and with the inherent difficulties to cross the blood brain barrier and attain the target sites. Despite the evidence that different classes of antioxidants are neuroprotectants in vitro, the clinical data is not consistent. Alzheimer's disease and antioxidant therapy is still an open question: the research is far from the end but the success may not be so time-consuming if the data obtained so far are gathered and rationally analyzed either by checking new targets or by the obtention of new and effective compounds, for instance by the rational modification of the previous ones.