Another Example of a Mitochondrially Targeted Antioxidant

Mitochondria, the powerplants of the cell, generate damaging reactive oxygen species as a side-effect of their operation. Unfortunately, they are vulnerable to those very same reactive compounds, and some forms of resulting damage to proteins and genes can create dysfunctional cells that contribute to degenerative aging. The longer you live, the more of these dysfunctional cells you have, and the larger their harmful effects.

This contribution to aging can be modestly slowed by use of antioxidants targeted to the mitochondria, as they will soak up some fraction of the oxidants generated before they cause damage. It is also the case that the effects of mitochondrial damage could be reversed entirely by some form of repair or replacement technology, and that would be a far better outcome.

Nonetheless, a number of research groups are working on targeted antioxidants, compounds that are very different from generic antioxidants sold in stores. Ingested antioxidants that you can buy today do nothing for this issue of mitochondrial damage, and are arguably a net negative for long-term health because they interfere with the signaling processes that produced increased cellular maintenance in response to exercise or other forms of mild stress.

Here is news of a recent addition to the research groups working on mitochondrially targeted antioxidants:

[Researchers] have designed a compound that suppresses symptoms of [Huntington's] disease in mice. The compound is a synthetic antioxidant that targets mitochondria, an organelle within cells that serves as a cell's power plant. Oxidative damage to mitochondria is implicated in many neurodegenerative diseases including Alzheimer's, Parkinson's, and Huntington's. The scientists administered the synthetic antioxidant, called XJB-5-131, to mice that have a genetic mutation that triggers Huntington's disease. The compound improved mitochondrial function and enhanced the survival of neurons. It also inhibited weight loss and stopped the decline of motor skills, among other benefits. In short, the Huntington's mice looked and behaved like normal mice.

Defending mitochondria from reactive oxygen species is a tall order. That's because mitochondria are both the main target of these molecules, and a cell's primary source of them. In other words, mitochondria produce the very thing that damages them. Researchers have studied whether dietary supplements of natural antioxidants such as vitamin E and coenzyme Q can mitigate the harmful effects of reactive oxygen species on mitochondria. Natural antioxidants don't target specific tissue within the body, however. And they've been shown to yield only marginal benefits in human clinical trials. These lackluster results have driven scientists to develop synthetic antioxidants that specifically target mitochondria. A few years ago, [researchers] synthesized an antioxidant called XJB-5-131 that zeroes in on bacterial membranes, which are very similar to mitochondrial membranes.

The scientists first injected Huntington's mice with XJB-5-131 and tested the mice's motor skills. ... We saw improvements across the board. The difference was amazing. XJB prevented the onset of weight loss and the decline in motor skills.

Next, the researchers removed neurons from the Huntington's mice and cultured the cells in the presence of XJB-5-131. They found that XJB-5-131 significantly improved the survival of neuronal cultures compared to untreated neuronal cultures. [Researchers] studied the impacts of the compound on the mice's mitochondrial DNA. They discovered that XJB-5-131 dramatically lowered the number of lesions on the DNA, which is a sign of oxidative damage. They also tallied the number of mitochondrial DNA copies, which plummets in diseased mice. This number was restored back to normal in XJB-treated mice.

Link: http://medicalxpress.com/news/2012-11-scientists-therapy-huntington-disease.html