Antioxidants Useful in Battle Against Alzheimer’s

19/01/07 New research suggests that oxidative stress – which results from an accumulation of free radicals – is involved in the neurodegeneration observed in dementias such as Alzheimer’s and Parkinson’s diseases, whilst the administration of anti-oxidants has the opposite effect and so might help in the control of these types of diseases. The research done by Doras Dias-Santagata, a Portuguese scientist, and colleagues, just published in the “Journal of Clinical Investigation” is exciting news for neurodegenerative patients all over the world.

Fruit becomes brown and butter becomes rancid - these are some of the everyday effects of oxidative stress. Free radicals are highly reactive molecules that result from the body energy producing mechanisms, and which are capable of oxidising and damaging DNA, proteins and cells in general. Oxidative stress (OS) by free radicals is fast becoming the medical buzzword, with a growing number of diseases, from cancer to cataracts or just ageing, associated with it. Under normal circumstances the body is capable of neutralising free radicals by producing anti-oxidants but in modern societies things are not that balanced anymore. In fact, environmental factors and changes in our lifestyles, which have lead to exposure to higher levels of pollution and poor quality diets, mean that we are exposed to free radicals more than ever before. Brain cells are known to be specially sensitive to degeneration by these molecules and, worryingly, signs of OS have already been found in the brains of patients with several neurodegenerative dementias such as Parkinson's, Alzheimer’ and Huntington's disease. However, whether OS is a cause or a result of disease is not clear.

To answer this question Dora Dias-Santagata, Mel B. Feany and colleagues at Brigham and Women’s Hospital and Harvard Medical School in Boston and Howard University in Washington decided to analyse the effect of different levels of oxidative stress in an Alzheimer’s model of fruit flies. In fact, most neurodegenerative dementias are characterised by having around the destroyed brain areas abnormal deposits of proteins which are believed to participate in the neurodegeneration. Dias-Santagata’s flies have been mutated to have aberrant deposits of one such protein, tau (found in Alzheimer’s brains) and show large destructed areas in their nervous system.

The team of researchers used two different approaches while testing OS effects in the fruit flies: on one hand they manipulated genes responsible for the production of anti-oxidant proteins and on the other hand administered vitamin E, a powerful anti-oxidant, to the mutant flies.

Dias-Santagata and colleagues found that reduction in the activity of two anti-oxidant proteins - SOD and Trxr – by genetic manipulation led to increasing neurodegeneration in the brain of the mutant flies, while administration of vitamin E had the opposite effect. Control flies without tau, and consequently no signs of neurodegeneration, were not affected by either the genetic or the pharmacological manipulation. Both results strongly suggest that oxidative stress plays an important role in neurodegenerative dementias, at least in those where tau is involved, and if controlled can help controlling the disease. But they also indicate that, at least in this model, OS is not a primary cause for the illness.

Another interesting result of the study was to find that brain destruction in the mutated fruit flies was associated with activation of a stress-induced group of proteins called JNK. This needs to be further investigated but it might help to understand how and why neural cells die in these diseases.

In a world where more than 24 million people suffer from neurodegenerative dementias and where Alzheimer’s disease, which for now is incurable, affects more than 5% of men and women above 60 years old Dias-Santagata and colleagues’ results are very exciting. As lead author Dora Dias-Santagata says ''This is exciting because antioxidants may prove to be a good therapeutic approach to treat Alzheimer's disease and ameliorate human neurodegeneration.