A look at how resveratrol, a component of red wine, may be used to treat HD
Details on how resveratrol works
Resveratrol has a very simple chemical structure, which enables it to play a role in a wide range of biological activities. As a result, resveratrol is able to act upon many different systems within the body. The following are explanations of some of the mechanisms through which resveratrol may exert its effects:
- Heme oxygenase
Similar to resveratrol, an enzyme called heme oxygenase (HO) also decreases oxidative stress and inflammation. Because of this similarity, researchers hypothesized that resveratrol might take advantage of the mechanism HO uses to exert its beneficial effects. Sure enough, it was found that when resveratrol was administered to rats, the amount of HO around the rats’ nerve cells increased. This effect was dose-dependent, meaning that levels of HO increased as more resveratrol was administered. This connection between resveratrol and HO is important because HO is thought to protect nerve cells in several ways. In addition to being a powerful antioxidant, HO also produces several byproducts that may assist in cell survival.
HO is involved in the regulation of the cellular uptake and storage of iron. Iron levels must be tightly regulated because adequate amounts of iron are essential for cellular functions, but excessive amounts of iron can lead to the formation of a reactive oxygen species (ROS), which is a highly reactive free radical. When resveratrol increases the amount of HO, higher levels of HO probably also affect the level of iron in the cells. Thus, one way resveratrol may exert its neuroprotective effects is by stimulating HO to balance out iron levels and protect from iron-mediated toxicity.
Although the connections between resveratrol, HO, and CO are quite intriguing, further research is needed to determine the exact details of how these compounds may work together to protect nerve cells. Nevertheless, these findings are encouraging for people with HD because if researchers are able to discover how nerve cells can be protected, then they may be able to develop treatments that could counteract the nerve cell damage caused by HD.
- MAP kinase
Several studies indicate that resveratrol activates two mitogen-activated protein (MAP) kinase family members. MAP kinases are important in communicating information and relaying messages within cells. In people with HD, the nerve cells are not very good at communicating and relaying messages to each other, and this inability to transfer information is one of the factors that causes the cells to die. Thus, MAP kinases may help delay the onset and progression of HD symptoms by helping the cells communicate with each other and enabling the cells to stay alive longer. In rat studies, low and moderate doses of resveratrol were able to significantly induce MAP kinase activation in rat brains. However, with high doses of resveratrol, activation of the MAP kinases was inhibited. This finding underscores the importance of the fact that even though a substance may be useful, every increase in dosage may not be accompanied by an increase in usefulness. It is unclear how resveratrol leads to the activation of the MAP kinase pathways and much more research needs to be done.
- Sirtuins
Researchers at Harvard University have demonstrated in yeast and fruit flies that resveratrol activates a group of enzymes called sirtuins, which extend the lifespans of these organisms. The effects of resveratrol mimic the effects of caloric restriction, which is to-date the only proven way of extending maximum lifespan. Even though the research has only been done in yeast, flies, and worms so far, the researchers believe that humans have their own version of lifespan-extending sirtuin enzymes. They believe that resveratrol acts by increasing the amount of sirtuins in the body. Sirtuins protect cells by preventing the breakdown of the cells’ DNA and slowing the intercellular chain of events that culminate in apoptosis. Although the research in this area is certainly intriguing, it is important not to get too carried away. Some people have stated that this finding could lead to an anti-aging pill and that the lifespan of humans could be extended by as much as twenty years. In reality, the researchers merely found that resveratrol can mimic the effects of caloric restriction, which has been shown to combat oxidative stress and apoptosis. This is important because oxidative stress plays a major role in the degeneration and death of nerve cells for people with HD. By fighting against oxidative stress and prolonging the life of nerve cells, reseveratrol may help to delay the onset and progression of HD symptoms.
Last Modified: 05/22/2009
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