Treatment With Vitamin C Dissolves Toxic Protein Aggregates In Alzheimer’s Disease

Katrin Mani, MD, PhD, Assistant Professor.

Researchers at Lund University in Sweden have discovered a new function for vitamin C. Treatment with vitamin C can dissolve the toxic protein aggregates that build up in the brain in Alzheimer’s disease. The research findings are now being presented in the Journal of Biological Chemistry.

The brains of people with Alzheimer’s disease contain lumps of so-called amyloid plaques which consist of misfolded protein aggregates. They cause nerve cell death in the brain and the first nerves to be attacked are the ones in the brain’s memory centre.

“When we treated brain tissue from mice suffering from Alzheimer’s disease with vitamin C, we could see that the toxic protein aggregates were dissolved. Our results show a previously unknown model for how vitamin C affects the amyloid plaques”, says Katrin Mani, reader in Molecular Medicine at Lund University.

“Another interesting finding is that the useful vitamin C does not need to come from fresh fruit. In our experiments, we show that the vitamin C can also be absorbed in larger quantities in the form of dehydroascorbic acid from juice that has been kept overnight in a refrigerator, for example”.

There is at present no treatment that cures Alzheimer’s disease, but the research is aimed at treatments and methods to delay and alleviate the progression of the disease by addressing the symptoms.

That antioxidants such as vitamin C have a protective effect against a number of diseases, from the common cold to heart attacks and dementia, has long been a current focus of research.

“The notion that vitamin C can have a positive effect on Alzheimer’s disease is controversial, but our results open up new opportunities for research into Alzheimer’s and the possibilities offered by vitamin C”, says Katrin Mani.

 

Reference

Cheng F, Cappai R, Ciccotosto GD, Svensson G, Multhaup G, Fransson LÅ, Mani K. Suppression of Amyloid β A11 Antibody Immunoreactivity by Vitamin C: POSSIBLE ROLE OF HEPARAN SULFATE OLIGOSACCHARIDES DERIVED FROM GLYPICAN-1 BY ASCORBATE-INDUCED, NITRIC OXIDE (NO)-CATALYZED DEGRADATION. J Biol Chem 2011; 286 (31): 27559-72.

 

Scientists Discover New Role For Vitamin C In The Eye — And The Brain

In a surprising finding, vitamin C is found to prolong proper functioning of retinal cells:

Portland, Ore. — Nerve cells in the eye require vitamin C in order to function properly — a surprising discovery that may mean vitamin C is required elsewhere in the brain for its proper functioning, according to a study by scientists at Oregon Health & Science University recently published in the Journal of Neuroscience.

“We found that cells in the retina need to be ‘bathed’ in relatively high doses of vitamin C, inside and out, to function properly,” said Henrique von Gersdorff, Ph.D., a senior scientist at OHSU’s Vollum Institute and a co-author of the study. “Because the retina is part of the central nervous system, this suggests there’s likely an important role for vitamin C throughout our brains, to a degree we had not realized before.”

The brain has special receptors, called GABA-type receptors, that help modulate the rapid communication between cells in the brain. GABA receptors in the brain act as an inhibitory “brake” on excitatory neurons in the brain. The OHSU researchers found that these GABA-type receptors in the retinal cells stopped functioning properly when vitamin C was removed.

Because retinal cells are a kind of very accessible brain cell, it’s likely that GABA receptors elsewhere in the brain also require vitamin C to function properly, von Gersdorff said. And because vitamin C is a major natural antioxidant, it may be that it essentially ‘preserves’ the receptors and cells from premature breakdown, von Gersdorff said.

The function of vitamin C in the brain is not well understood. In fact, when the human body is deprived of vitamin C, the vitamin stays in the brain longer than anyplace else in the body. “Perhaps the brain is the last place you want to lose vitamin C,” von Gersdorff said. The findings also may offer a clue as to why scurvy — which results from a severe lack of vitamin C — acts the way it does, von Gersdorff said. One of the common symptoms of scurvy is depression, and that may come from the lack of vitamin C in the brain.

The findings could have implications for other diseases, like glaucoma and epilepsy. Both conditions are caused by the dysfunction of nerve cells in the retina and brain that become over excited in part because GABA receptors may not be functioning properly.

“For example, maybe a vitamin C-rich diet could be neuroprotective for the retina — for people who are especially prone to glaucoma,” von Gersdorff said. “This is speculative and there is much to learn. But this research provides some important insights and will lead to the generation of new hypotheses and potential treatment strategies.”

Scientists and students in von Gerdorff’s lab in OHSU’s Vollum Institute are dedicated to basic neuroscience research. The vitamin C research work was done using goldfish retinas, which have the same overall biological structure as human retinas.

 

Reference

Calero CI, Vickers E, Moraga Cid G, Aguayo LG, von Gersdorff H, Calvo DJ.  Allosteric Modulation of Retinal GABA Receptors by Ascorbic Acid. J Neurosci 2011;31 (26): 9672-82.

Vitamin C: A Potential Life-saving Treatment For Sepsis

Physicians caring for patients with sepsis may soon have a new safe and cost-effective treatment for this life-threatening illness. Research led by Dr. Karel Tyml and his colleagues at The University of Western Ontario and Lawson Health Research Institute have found that vitamin C can not only prevent the onset of sepsis, but can reverse the disease.

Sepsis is caused by a bacterial infection that can begin anywhere in your body. Your immune system goes into overdrive, overwhelming normal processes in your blood. The result is that small blood clots form, blocking blood flow to vital organs. This can lead to organ failure. Babies, the elderly and those with weakened immune systems are most likely to get sepsis. But even healthy people can become deathly ill from the disease.

According to Dr. Tyml, a professor at Western’s Schulich School of Medicine & Dentistry, patients with severe sepsis have a high mortality rate, nearly 40 percent, because there is no effective treatment.

“There are many facets to sepsis, but the one we have focused on for the past 10 years is the plugging of capillaries,” says Dr. Tyml. Plugged capillaries prevent oxygenation and the supply of life-supporting materials to your organ tissue and stop the removal of metabolic waste product. Plugged capillaries are seen in organs of septic patients. These organs may eventually fail, leading to multiple organ failure and death. Dr. Tyml’s lab was the first to discover this plugging by using intravital microscopy, a technique Dr. Tyml pioneered in Canada.

According to Dr. Tyml’s most recent publication, oxidative stress and the activated blood clotting pathway are the major factors responsible for the capillary plugging in sepsis. Through his research, Dr. Tyml has discovered that a single bolus of vitamin C injected early at the time of induction of sepsis, prevents capillary plugging. He has also found that a delayed bolus injection of vitamin C can reverse plugging by restoring blood flow in previously plugged capillaries.

“Our research in mice with sepsis has found that early as well as delayed injections of vitamin C improves chance of survival significantly,” explains Dr. Tyml. “Furthermore, the beneficial effect of a single bolus injection of vitamin C is long lasting and prevents capillary plugging for up to 24 hours post-injection.”

Dr. Tyml and his colleagues are eager to find appropriate support to move this research from the bench to the bedside to see if these findings translate to patients with sepsis.

The potential benefit of this treatment is substantial. “Vitamin C is cheap and safe. Previous studies have shown that it can be injected intravenously into patients with no side effects,” says Dr. Tyml. “It has the potential to significantly improve the outcome of sepsis patients world-wide. This could be especially beneficially in developing countries where sepsis is more common and expensive treatments are not affordable.”
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