Team finds connection in pathogenesis of neurological diseases, HIV

February 4, 2014

A new study by George Washington University (GW) researcher Michael Bukrinsky, M.D., Ph.D., shows similarities in the pathogenesis of prion disease—misfolded proteins that can lead to neurological diseases—and the HIV virus.

The research, published in the Journal of Biological Chemistry, looks at the relationship between cholesterol metabolism and infection as a follow-up to previous research on the relationship between cholesterol metabolism and HIV. Bukrinsky, a professor of microbiology, immunology, and tropical medicine at the GW School of Medicine and Health Sciences, and his research team found a striking relationship between impairment of cellular cholesterol transporter ABCA1 and the conversion of prion into the pathological form, which occurs in lipid rafts – the membrane domains of .

"The effect of prions on ABCA1 and lipid rafts is very similar to what we found with HIV before, suggesting that while prions and viruses are very different, they seem to target the same cellular mechanism of cholesterol metabolism," said Bukrinsky. "This mechanism may be key to controlling many different diseases. It may be that drugs that stimulate ABCA1 can help not only to target prions and HIV, but also a number of other pathogens."

Under normal circumstances, an abundance of ABCA1 limits the number of lipid rafts – and vice versa. With prions, the opposite effect takes place. During the conversion of prions into a pathogenic form, an abundance of ABCA1 in cells increases, but so does the amount of lipid rafts. The reason for this paradox is that ABCA1 in prion-infected cells is non-functional. The researchers found that ABCA1 was displaced from the plasma membrane and from lipid rafts by prions and was internalized, inhibiting its function. Stimulation of ABCA1 with drugs inhibited conversion of prions from non-pathogenic to pathogenic form, reducing the number of in the cell, and opening the possibility of treating with these drugs.

Bukrinsky and his research team also found that when cells are loaded with cholesterol, it likewise counteracts this effect of prions on ABCA1 and in a cell. While in most circumstances having lots of lipids and fats in one's diet is not recommended, this finding suggests that being loaded with fat actually stops the conversion of prions from the non-pathogenic to pathogenic form. Neuronal cells loaded with lipids are actually less prone to becoming susceptible to prion disease. "This isn't a recommendation as we are talking about a very specific cell type and under special circumstances," said Bukrinsky, "but it's an interesting possibility."

Explore further: New yeast prion helps cells survive

More information: The paper, titled "Prion Infection Impairs Cholesterol Metabolism in Neuronal Cells" is available online at www.jbc.org/content/early/2013 … M113.535807.abstract

Related Stories

New yeast prion helps cells survive

April 23, 2012
One of the greatest mysterious in cellular biology has been given a new twist thanks to findings reported in Science. Researchers at the RIKEN Brain Science Institute show that prions, proteins that transmit heritable information ...

Cellular stress can induce yeast to promote prion formation

July 23, 2011
It's a chicken and egg question. Where do the infectious protein particles called prions come from? Essentially clumps of misfolded proteins, prions cause neurodegenerative disorders, such as mad cow/Creutzfeld-Jakob disease, ...

Recombinant human prion protein inhibits prion propagation

October 9, 2013
Case Western Reserve University researchers today published findings that point to a promising discovery for the treatment and prevention of prion diseases, rare neurodegenerative disorders that are always fatal. The researchers ...

Recommended for you

Study reveals key molecular link in major cell growth pathway

October 19, 2017
A team of scientists led by Whitehead Institute has uncovered a surprising molecular link that connects how cells regulate growth with how they sense and make available the nutrients required for growth. Their work, which ...

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

Tracing cell death pathway points to drug targets for brain damage, kidney injury, asthma

October 19, 2017
University of Pittsburgh scientists are unlocking the complexities of a recently discovered cell death process that plays a key role in health and disease, and new findings link their discovery to asthma, kidney injury and ...

Inflammation trains the skin to heal faster

October 18, 2017
Scars may fade, but the skin remembers. New research from The Rockefeller University reveals that wounds or other harmful, inflammation-provoking experiences impart long-lasting memories to stem cells residing in the skin, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.