Potatoes May Hold Key To Alzheimer's Treatment

A virus that commonly infects potatoes bears a striking resemblance to one of the key proteins implicated in Alzheimer's disease (AD), and researchers have used that to develop antibodies that may slow or prevent the onset of AD.

Studies in mice have demonstrated that vaccinations with the amyloid beta protein (believed to be a major AD contributor) to produce A antibodies can slow disease progression and improve cognitive function, possibly by promoting the destruction of amyloid plaques. Some early human trials have likewise been promising, but had to be halted due to the risk of autoimmune encephalitis.

One way to make Alzheimer's vaccinations safer would be to use a closely-related, but not human, protein as the vaccine, much like cowpox virus is used for smallpox immunizations.

In the August 15 Journal of Biological Chemistry, Robert Friedland and colleagues used this concept on an amyloid-like protein found in potato virus (PVY). They injected PVY into mice followed by monthly boosters for four months. The researchers found that the mice produced strong levels of antibodies that could attach to amyloid beta protein both in both solution and in tissue samples of Alzheimer's patients. And although the levels were lower, mice also developed A antibodies if given injections of PVY-infected potato leaf as opposed to purified PVY.

Friedland and colleagues note that potato virus is a fairly common infection that poses no risk to humans (many people have probably eaten PVY infected potatoes). While tests of PVY antibodies will ultimately determine how useful they can be, they may be a promising lead to treating this debilitating disease.

How corals adapt to day and night

Researchers have uncovered a gene in corals that responds to day/night cycles, which provides some tantalizing clues into how symbiotic corals work together with their plankton partners.

Corals are fascinating animals that form the largest biological constructions in the world, sprawling coral reefs that cover less than 0.2 % of the seafloor yet provide habitats for more than 30% of marine life. In shallow waters that don't have abundant food, corals have developed a close relationship with small photosynthetic critters called dinoflagellates. The dinoflagellates use sunlight to produce energy for the coral, which in turn use that energy to construct mineralized skeletons for protection. The mineral production, known as coral calcification, is closely tied with the day/night cycle, though the molecular mechanism behind this synchronization is mysterious.

Aurelie Moya and colleagues have now characterized the first coral gene that responds to the light cycle; this gene, called STPCA, makes an enzyme that converts carbon dioxide to bicarbonate (baking soda) and is twice as active at night compared to daytime. The researchers found that the enzyme concentrates in the watery layer right under the calcified skeleton, which combined with studies showing that STPCA inhibitors lower calcification rates, confirms a direct role for STPCA in this process.

Moya and colleagues propose that STPCA becomes more active at night to cope with acid buildup. The calcification process requires many hydrogen atoms, which during the day can be removed by photosynthesis; at night, however, hydrogen accumulates which increases the acidity of the coral, and therefore STPCA creates extra bicarbonate as a buffer to prevent acid damage.

Purifying parasites with light

Researchers have developed a clever method to purify parasitic organisms from their host cells, which will allow for more detailed proteomic studies and a deeper insight into the biology of organisms that cause millions of cases of disease each year.

Many infectious pathogens, like those that cause Toxoplasmosis or Leishmaniases, have a complex life cycle alternating between free-living creature and cell-enclosed parasite. A thorough analysis of the proteins that help these organisms undergo this lifestyle change would be tremendously useful for drug or vaccine development; however, it's extremely difficult to separate the parasites from their host cell for detailed study.

As reported in the September Molecular & Cellular Proteomics, Toni Aebischer and colleagues worked around this problem by designing special fluorescent Leishmania mexicana (one of the many Leishmaniases parasites). They then passed infected cells through a machine that can separate cell components based on how much they glow. Using this approach, the researchers separated the Leishmania parasites with only about 2% contamination, far better than current methods.

They then successfully identified 509 proteins in the parasites, 34 of which were more prominent in parasites than free living Leishmania. The results yielded many characteristics of these organisms, such as a high presence of fatty acid degrading enzymes, which highlights adaptation to intracellularly available energy sources. The identified proteins should provide a good data set for continued selection of drug targets, and the success of this method should make it a good resource for other cellular parasites like malaria.

Tuberculosis drug shows promise against latent bacteria

A new study has shown that an investigational drug (R207910, currently in clinical trials against multi-drug resistant tuberculosis strains) is quite effective at killing latent bacteria. This revelation suggests that R207910 may lead to improved and shortened treatments for this globally prevalent disease.

Despite numerous treatment advances, tuberculosis (TB) remains a serious disease fueled by co-infection of HIV patients, the rise of drug-resistant strains, and the ability of Mycobacterium tuberculosis to become dormant and linger in the lungs. In fact, one third of the world population is infected, asymptomatically, with latent TB and is at risk of developing active TB disease during their life time.

Anil Koul and colleagues at Johnson & Johnson tested R207910 on dormant M. tuberculosis in three different laboratory models of latency. R207910 targets a protein (ATP synthase) essential for making cellular energy (ATP) in actively replicating TB. The researchers reasoned that even dormant bacteria, which are essentially physiologically "turned off", still need to produce small quantities of ATP to survive. As such, a block in ATP synthesis might be an Achilles heel for killing dormant bacteria.

This reasoning proved to be correct and R207190 was able to kill dormant bacteria by greater than 95% whereas current drugs like isoniazid had no effect. Surprisingly, they found that R207910 is slightly more effective in killing dormant bacteria as compared to actively replicating ones, a unique spin as all known TB drugs are more effective on replicating bugs. Koul and colleagues hope to validate these results clinically, and note that ATP synthase should be looked at as a drug target for other persistent bacterial infections.