Read with caution!
This post was written during early stages of trying to understand a complex scientific problem, and we didn't get everything right. The original author no longer endorses the content of this post. It is being left online for historical reasons, but read at your own risk.
Despite Coenzyme Q in the title, Martin 2007 ”Coenzyme Q and protein/lipid oxidation in a BSE-infected transgenic mouse model” is not a study of the dietary supplement CoQ10 as a therapeutic agent for prion infections, as is being explored for Huntington’s Disease. Rather, it is a characterization of lipid and protein oxidation, and the physiological Coenzyme Q response to this stress, over the course of prion disease in mice.
This study used BoPrP-Tg110 transgenic mice expressing cow PrP, infected intracerebrally with brain homogenate from BSE-infected cows. The mice were sacrificed at a variety of points throughout the disease course so that biochemistry and immunohistochemistry could be used to determine the extent of oxidative damage and the mouse’s Coenzyme Q response to it. As background, the incubation time in these mice is relatively long (compared to other scrapie-infected mouse models): the mice showed clinical signs between 250 and 290 dpi, and they all had to be sacrificed due to advanced disease between 300 and 320 dpi.
The result of the experiment was that the mice do not show significantly elevated oxidation during the ~290 days of asymptomatic incubation period. Only during the month or so of full-blown disease at the end of life did the mice show approximately double the level of protein and lipid oxidation compared to controls. But interestingly, levels of two varieties of Coenzyme Q (CoQ9 and CoQ10) were elevated in the infected mice starting about 150 dpi, reaching approximately double the levels in control mice. Chronologically, this was almost coincident with the beginning of PrP-res plaque deposition and observable pathological changes in the brain, consistent with the idea that CoQ was elevated in response to the infection really taking hold and beginning to do damage. So even though elevated oxidation was not observed until ~290 dpi, the suspicion is that the prion infection did cause oxidative stress early on, but that the mice were able to respond to this by upregulating CoQ, an antioxidant, to contain the damage.
The fact that significant oxidation of lipids and proteins occurred late in the disease, and that it looks like it might have happened earlier if not for the CoQ response, is consistent with the apparently well-established role for oxidative stress in Alzheimer’s, Parkinson’s, and so on.
Since CoQ is already physiologically upregulated in response to prion infection and, after all, doesn’t stop the disease, you could argue CoQ10 wouldn’t do much good as a prion therapeutic. On the other hand, since oxidative damage is a feature of prion disease, and it looks like CoQ is part of the body’s endogenous response to it, you could argue that adding exogenous CoQ10 might help. The authors come down slightly on the latter side, saying “we propose a future therapeutic study of the development of prion disease based on the administration of a cocktail of CoQ-related chemical agents including CoQ”. By “related chemical agents” they are referring to other antioxidants (including curcumin and Vitamin C) and metal chelators. Blood-brain barrier penetration of CoQ10 is described as “very poor”, so they’re interested in other molecules that could cross more easily and have the same effect.
What the article doesn’t address, that I would have been most curious about, is the role of oxidation in triggering spontaneous prion disease. It is an open question not just for genetic prion diseases but for all age-onset genetic diseases why the disease only emerges late in life even though the mutation is always present. Because oxidation is one of the central processes of what we call aging, there is plenty of speculation that oxidation provides some sort of trigger. But to my knowledge no one has yet provided convincing molecular evidence for what exactly that trigger might consist of.