Artificial Sweetener ( Mannitol ) a Potential Treatment for Parkinson’s Disease

Monday, June 17, 2013

TAU researcher says mannitol could prevent aggregation of toxic proteins in the brain

Mannitol, a sugar alcohol produced by fungi, bacteria, and algae, is a common component of sugar-free gum and candy. The sweetener is also used in the medical field — it’s approved by the FDA as a diuretic to flush out excess fluids and used during surgery as a substance that opens the blood/brain barrier to ease the passage of other drugs.

Now Profs. Ehud Gazit and Daniel Segal of Tel Aviv University’s Department of Molecular Microbiology and Biotechnology and the Sagol School of Neuroscience, along with their colleague Dr. Ronit Shaltiel-Karyo and PhD candidate Moran Frenkel-Pinter, have found that mannitol also prevents clumps of the protein α-synuclein from forming in the brain — a process that is characteristic of Parkinson’s disease.

These results, published in the Journal of Biological Chemistry and presented at the Drosophila Conference in Washington, DC in April, suggest that this artificial sweetener could be a novel therapy for the treatment of Parkinson’s and other neurodegenerative diseases. The research was funded by a grant from the Parkinson’s Disease Foundation and supported in part by the Lord Alliance Family Trust.

Seeing a significant difference

After identifying the structural characteristics that facilitate the development of clumps of α-synuclein, the researchers began to hunt for a compound that could inhibit the proteins’ ability to bind together. In the lab, they found that mannitol was among the most effective agents in preventing aggregation of the protein in test tubes. The benefit of this substance is that it is already approved for use in a variety of clinical interventions, Prof. Segal says.

Next, to test the capabilities of mannitol in the living brain, the researchers turned to transgenic fruit flies engineered to carry the human gene for α-synuclein. To study fly movement, they used a test called the “climbing assay,” in which the ability of flies to climb the walls of a test tube indicates their locomotive capability. In the initial experimental period, 72 percent of normal flies were able to climb up the test tube, compared to only 38 percent of the genetically-altered flies.

The researchers then added mannitol to the food of the genetically-altered flies for a period of 27 days and repeated the experiment. This time, 70 percent of the mutated flies could climb up the test tube. In addition, the researchers observed a 70 percent reduction in aggregates of α-synuclein in mutated flies that had been fed mannitol, compared to those that had not.

These findings were confirmed by a second study which measured the impact of mannitol on mice engineered to produce human α-synuclein, developed by Dr. Eliezer Masliah of the University of San Diego. After four months, the researchers found that the mice injected with mannitol also showed a dramatic reduction of α-synuclein in the brain.

Delivering therapeutic compounds to the brain

The researchers now plan to re-examine the structure of the mannitol compound and introduce modifications to optimize its effectiveness. Further experiments on animal models, including behavioral testing, whose disease development mimics more closely the development of Parkinson’s in humans is needed, Prof. Segal says.

For the time being, mannitol may be used in combination with other medications that have been developed to treat Parkinson’s but which have proven ineffective in breaking through the blood/brain barrier, says Prof. Segal. These medications may be able to “piggy-back” on mannitol’s ability to open this barrier into the brain.

Although the results look promising, it is still not advisable for Parkinson’s patients to begin ingesting mannitol in large quantities, Prof. Segal cautions. More testing must be done to determine dosages that would be both effective and safe

Indian plant could play key role in death of cancer cells

Contact: Danielle Moores dwongmoores@yahoo.com 706-496-5956 Georgia Health Sciences University

AUGUSTA, Ga. – Scientists at the Georgia Regents University Cancer Center have identified an Indian plant, used for centuries to treat inflammation, fever and malaria, that could help kill cancer cells.

Cancer cells typically avoid death by hijacking molecular chaperones that guide and protect the proteins that ensure normal cellular function and then tricking them into helping mutated versions of those proteins stay alive, says Dr. Ahmed Chadli, a researcher in the Molecular Chaperone Program at the GRU Cancer Center and senior author of the study named the Journal of Biological Chemistry‘s Paper of the Week.

Drug development has focused on the chaperone Hsp90 (heat shock protein 90) because it plays a key role in assisting mutated proteins, making it an attractive cancer drug target. However, the clinical efficacy of Hsp90 inhibitors has been disappointing. Most current small molecules targeting Hsp90 have inadvertently resulted in the expression of proteins that protect cancer cells from programmed cell death and compromise the Hsp90 inhibitors in the clinic.

In this study, however, Chaitanya Patwardhan, a graduate student in Dr. Chadli’s lab, found that gedunin, an Indian plant compound, attacks a co-chaperone, or helper protein, of Hsp90 called p23.

“This compound binds directly to p23, leading to inactivation of the Hsp90 machine—without production of anti-apoptotic proteins—thus killing cancer cells,” said Dr. Chadli. “The idea here is that this will open a door for new ways of targeting Hsp90 by targeting its helper proteins, which may be used in combination with established Hsp90 inhibitors that are ongoing clinical trials. In the future, this research could have applications in drug development for hormone-dependent cancers, including breast, prostate and endometrial cancers.”

“One of the major areas of scientific emphasis of the GRU Cancer Center is to develop therapeutic approaches to cancer targeting specific molecules within the cancer cell, including chaperones,” said Dr. Samir N. Khleif, Director of the GRU Cancer Center. “This finding is an important piece of the puzzle, bringing us closer to our goal of helping patients with cancer.”

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Along with Patwardhan, the study was also authored by Dr. Abdul Fauq, Mayo Clinic College of Medicine; Laura B. Peterson and Dr. Brian S.J. Blagg, both of the University of Kansas; and Dr. Charles Miller, Tulane University School of Public Health and Tropical Medicine.

Dr. Chadli’s lab is also the recipient of a National Institutes of Health R01 grant to look for new molecules targeting the Hsp90 machine.

Only the top 2 percent of the 6,600 manuscripts annually reviewed in terms of significance and overall importance, by the JBC are ranked as Papers of the Week. The study will also be the focus of an upcoming JBC podcast.

Green tea and red wine extracts interrupt Alzheimer’s disease pathway in cells

Contact: Chris Bunting c.j.bunting@leeds.ac.uk 44-113-343-2049 University of Leeds

Natural chemicals found in green tea and red wine may disrupt a key step of the Alzheimer’s disease pathway, according to new research from the University of Leeds.

In early-stage laboratory experiments, the researchers identified the process which allows harmful clumps of protein to latch on to brain cells, causing them to die. They were able to interrupt this pathway using the purified extracts of EGCG from green tea and resveratrol from red wine.

The findings, published in the Journal of Biological Chemistry, offer potential new targets for developing drugs to treat Alzheimer’s disease, which affects some 800,000 people in the UK alone, and for which there is currently no cure.

“This is an important step in increasing our understanding of the cause and progression of Alzheimer’s disease,” says lead researcher Professor Nigel Hooper of the University’s Faculty of Biological Sciences. “It’s a misconception that Alzheimer’s is a natural part of ageing; it’s a disease that we believe can ultimately be cured through finding new opportunities for drug targets like this.”

Alzheimer’s disease is characterised by a distinct build-up of amyloid protein in the brain, which clumps together to form toxic, sticky balls of varying shapes. These amyloid balls  latch on to the surface of nerve cells in the brain by attaching to proteins on the cell surface called prions, causing the nerve cells to malfunction and eventually die.

“We wanted to investigate whether the precise shape of the amyloid balls is essential for them to attach to the prion receptors, like the way a baseball fits snugly into its glove,” says co-author Dr Jo Rushworth. “And if so, we wanted to see if we could prevent the amyloid balls binding to prion by altering their shape, as this would stop the cells from dying.”

The team formed amyloid balls in a test tube and added them to human and animal brain cells. Professor Hooper said: “When we added the extracts from red wine and green tea, which recent research has shown to re-shape amyloid proteins, the amyloid balls no longer harmed the nerve cells. We saw that this was because their shape was distorted, so they could no longer bind to prion and disrupt cell function.

“We also showed, for the first time, that when amyloid balls stick to prion, it triggers the production of even more amyloid, in a deadly vicious cycle,” he added.

Professor Hooper says that the team’s next steps are to understand exactly how the amyloid-prion interaction kills off neurons.

“I’m certain that this will increase our understanding of Alzheimer’s disease even further, with the potential to reveal yet more drug targets,” he said.

Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, which part-funded the study, said: “Understanding the causes of Alzheimer’s is vital if we are to find a way of stopping the disease in its tracks. While these early-stage results should not be a signal for people to stock up on green tea and red wine, they could provide an important new lead in the search for new and effective treatments. With half a million people affected by Alzheimer’s in the UK, we urgently need treatments that can halt the disease – that means it’s crucial to invest in research to take results like these from the lab bench to the clinic.”

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The research was funded by the Wellcome Trust, Alzheimer’s Research UK and the Medical Research Council.

Further information

For interviews, please contact Chris Bunting, Press Officer, University of Leeds; phone 0113 343 2049, email c.j.bunting@leeds.ac.uk

The Full Paper:  Jo V. Rushworth, Heledd H. Griffiths, Nicole T. Watt and Nigel M. Hooper, ‘Prion protein-mediated neurotoxity of amyloid-β oligomers requires lipid rafts and the transmembrane LRP1,’ Journal of Biological Chemistry [DOI:10.1074/jbc.M112.400358] is available at http://www.jbc.org/content/early/2013/02/06/jbc.M112.400358.full.pdf+html from 6pm (EST), February 5.  Copies of the paper are available on request from the University of Leeds press office.

Notes for editors:

1. Nigel Hooper is Professor of Biochemistry at the University of Leeds. Further information about his research can be found here: http://www.fbs.leeds.ac.uk/staff/profile.php?un=bmbnmh

2. Alzheimer’s disease is the most common form of dementia, costing the UK economy £23 billion per year.  One in three people aged over 65 are expected to die with a form of dementia and 163,000 new cases are diagnosed in England and Wales each year. Worldwide, more than 35 million people are estimated to have dementia. (Source: www.alzheimersresearchuk.org )

3. University of Leeds, Faculty of Biological Sciences

The Faculty of Biological Sciences at the University of Leeds is one of the largest in the UK, with over 110 academic staff and over 400 postdoctoral fellows and postgraduate students. The Faculty is ranked 4th in the UK (Nature Journal, 457 (2009) doi:10.1038/457013a) based on results of the 2008 Research Assessment Exercise (RAE).  The RAE feedback noted that “virtually all outputs were assessed as being recognized internationally, with many (60%) being internationally excellent or world-leading” in quality. The Faculty’s research grant portfolio totals some £53M and funders include charities, research councils, the European Union and industry.  www.fbs.leeds.ac.uk

4. The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk

5. Alzheimer’s Research UK is the UK’s leading charity specialising in finding preventions, treatments and a cure for dementia. We are currently supporting dementia research projects worth over £20 million in leading Universities across the UK. To help us defeat dementia, donate today by visiting www.alzheimersresearchuk.org or calling 01223 843899.

6. For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including the first antibiotic penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk

Medicinal toothbrush tree yields antibiotic to treat TB in new way

Contact: Tony Maxwell zoe.dunford@nbi.ac.uk 44-160-345-0771 Norwich BioScience Institutes

A compound from the South African toothbrush tree inactivates a drug target for tuberculosis in a previously unseen way.

Tuberculosis causes more deaths worldwide than any other bacterial disease. At the same time as rates are increasing, resistance strains are emerging due, in part, to non-compliance with the treatment required. Many current drugs are nearly 50 years old and alternatives are needed to the long, demanding treatment schedules.

The compound under research, diospyrin, binds to a novel site on a well-known enzyme, called DNA gyrase, and inactivates the enzyme. DNA gyrase is essential for bacteria and plants but is not present in animals or humans. It is established as an effective and safe drug target for antibiotics.

“The way that diospyrin works helps to explain why it is effective against drug-sensitive and drug-resistant strains of tuberculosis,” said Professor Tony Maxwell from the John Innes Centre.

In traditional medicine the antibacterial properties of the tree are used for oral health and to treat medical complaints such bronchitis, pleurisy and venereal disease. Twigs from the tree are traditionally used as toothbrushes.

Most antibiotics originate from naturals sources, such as the soil bacteria Streptomyces. Antibiotics derived from plants are less common, but they are potentially rich sources of new medicines.

“Extracts from plants used in traditional medicine provide a source for novel compounds that may have antibacterial properties, which may then be developed as antibiotics,” said Professor Maxwell.

“This highlights the value of ethnobotany and the value of maintaining biodiversity to help us address global problems.”

The work on diospyrin and related naphthoquinone compounds is being continued by Professor Maxwell as part of the efforts of a consortium of European researchers, More Medicines For Tuberculosis (MM4TB). The collaboration between 25 labs across Europe is dedicated to the development of new drugs for TB.

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The work was carried out by postdoctoral researcher Fred Collin and will be continued by South African research assistant Natassja Bush. It is published in the Journal of Biological Chemistry: http://www.jbc.org/cgi/doi/10.1074/jbc.M112.419069.

Carnitine supplements reverse glucose intolerance in animals

2009 study posted for filing

Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center

DURHAM, N.C. – Supplementing obese rats with the nutrient carnitine helps the animals to clear the extra sugar in their blood, something they had trouble doing on their own, researchers at Duke University Medical Center report.

A team led by Deborah Muoio (Moo-ee-oo), Ph.D., of the Duke Sarah W. Stedman Nutrition and Metabolism Center, also performed tests on human muscle cells that showed supplementing with carnitine might help older people with prediabetes, diabetes, and other disorders that make glucose (sugar) metabolism difficult.

Carnitine is made in the liver and recycled by the kidney, but in some cases when this is insufficient, dietary carnitine from red meat and other animal foods can compensate for the shortfall.

After just eight weeks of supplementation with carnitine, the obese rats restored their cells’ fuel- burning capacity (which was shut down by a lack of natural carnitine) and improved their glucose tolerance, a health outcome that indicates a lower risk of diabetes.

These results offer hope for a new therapeutic option for people with glucose intolerance, older people, people with kidney disease, and those with type 2 diabetes (what used to be called adult-onset diabetes).

Muoio said that soon her team of researchers will begin a small clinical trial of carnitine supplementation in people who fit the profile of those who might benefit from additional carnitine – older people (60 to 80 years) with glucose intolerance.

The study is published in the Aug. 21 issue of the Journal of Biological Chemistry.

The Duke researchers began studying carnitine more closely when abnormalities in the nutrient emerged from blood chemistry profiles of obese and old animals. These chemical profiles report on hundreds of byproducts of cell metabolism called metabolites and give scientists an opportunity to identify markers of disease states.

Carnitine is a natural compound known for helping fatty acids enter the mitochondria, the powerhouses of cells, where fatty acids are “burned” to give cells energy for their various tasks. Carnitine also helps move excess fuel from cells into the circulating blood, which then redistributes this energy source to needier organs or to the kidneys for removal. These processes occur through the formation of acylcarnitine molecules, energy molecules that can cross membrane barriers that encase all cells.

Researchers at Duke had observed that skeletal muscle of obese rats produced high amounts of the acylcarnitines, which requires free carnitine. As these molecules started to accumulate, the availability of free, unprocessed carnitine decreased. This imbalance was linked to fuel-burning problems, that is, impairments in the cells’ combustion of both fat and glucose fuel.

“We suspected that persistent increases in acylcarnitines in the rats were causing problems, and we could also see that the availability of free carnitine was decreasing with weight gain and aging,” said Muoio. “It appeared that carnitine could no longer do its job when chronic metabolic disruptions were stressing the system. That’s when we designed an experiment to add extra carnitine to the rats’ diet.”

Muoio is also a professor in the departments of medicine, pharmacology and cancer biology.

 

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Other study authors included Robert C. Noland, Sarah E. Seiler, Helen Lum, Olga Ilkayeva, Robert Stevens, and Timothy R. Koves of the Sarah W. Stedman Nutrition and Metabolism Center. Koves is also with the Duke Department of Medicine. Robert M. Lust is with the Department of Physiology at East Carolina University in Greenville, N.C., and Fausto G. Hegardt is with the CIBER division Fisiopatología de la Obesidad y la Nutrición of the Instituto de Salud Carlos III in Spain.

The work was supported by grants from the National Institutes of Health, and the American Diabetes Association, and a John A. Hartford Duke Center for Excellence Award

Selenium may slow march of AIDS

2008 study posted for filing

Contact: Amitabh Avasthi
axa47@psu.edu
814-865-9481
Penn State

Increasing the production of naturally occurring proteins that contain selenium in human blood cells slows down multiplication of the AIDS virus, according to biochemists.

“We have found that increasing the expression of proteins that contain selenium negatively affects the replication of HIV,” said K. Sandeep Prabhu, Penn State assistant professor of immunology and molecular toxicology. “Our results suggest a reduction in viral replication by at least 10-fold.”

Selenium is a micronutrient that the body needs to maintain normal metabolism. Unlike other nutrients, which bind to certain proteins and modulate the protein’s activity, selenium gets incorporated into proteins in the form of an amino acid called selenocysteine.

These proteins – selenoproteins – are especially important in reducing the stress caused by an infection, thereby slowing its spread.

Upon infecting a person, the virus quickly degrades selenoproteins so that it can replicate efficiently. It is unclear just how the virus is able to silence these proteins but Prabhu and his colleagues believe that stress inflicted on cells by the rapidly dividing virus, which produces a key protein known as Tat, is the likely culprit.

Tat is one of about 14 odd proteins produced by HIV during the first stage of infection. The job of these proteins is to trigger the expression of all the other genes that the virus needs to sustain itself. In addition, Tat also plays a key role in helping the virus replicate.

One of the proteins that targets Tat is a selenoprotein known as TR1.

“Since HIV targets the selenoproteins, we thought that the logical way to deal with the virus is to increase the expression of such proteins in the body,” explained Prabhu, whose team’s findings are outlined this week (Nov. 28) in the Journal of Biological Chemistry.

Researchers first isolated blood cells from healthy human volunteers who did not have HIV, and infected those cells with the virus. Next, they added tiny amounts of a selenium compound – sodium selenite – into the cell culture to see the effect on viral replication.

Results from the tests indicate that the addition of selenium inhibits the replication of HIV at least 10-fold, compared to cell cultures in which no selenium is added. When the researchers selectively reduced production of the selenium containing TR1 protein, they observed a 3.5-fold increase in viral replication.

“This confirms that while increasing the expression of TR1 has a negative impact on the replication of HIV, reducing it helps the virus replicate more efficiently,” explained Prabhu. He believes that TR1 works by upsetting the chemical structure of Tat, which in turn reduces the virus’ ability to replicate.

“Once we fully understand the function of these selenium proteins, it will give us a handle to come up with more effective drugs,” said Prabhu, whose work is partly funded by the National Institutes of Health.

 

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Other researchers on the paper include Parisa Kalantari, post-doctoral scholar; Vivek Narayan, graduate student; Kambadur Muralidhar, visiting faculty; Ujjawal H. Gandhi, graduate student; and Hema Vunta, graduate student, all at Penn State; Satish K. Natarajan, research associate, University of Nebraska; and Andrew J. Henderson, associate professor of medicine and microbiology, Boston University.

 

Scientists discover one of the ways the influenza virus disarms host cells

Contact: Megan Fellman fellman@northwestern.edu 847-491-3115 Northwestern University

Advantage flu virus

When you are hit with the flu, you know it immediately — fever, chills, sore throat, aching muscles, fatigue. This is your body mounting an immune response to the invading virus. But less is known about what is happening on the molecular level.

Now Northwestern University scientists have discovered one of the ways the influenza virus disarms our natural defense system. The virus decreases the production of key immune system-regulating proteins in human cells that help fight the invader. The virus does this by turning on the microRNAs — little snippets of RNA — that regulate these proteins.

The researchers, led by molecular biologist Curt M. Horvath, are among the first to show the influenza virus can change the expression of microRNA to control immune responses in human lung cells.

The findings reveal a new aspect of the interaction between the influenza virus and its host. Knowing how viruses disable the immune system to wreak havoc in the body will help researchers design therapeutics to preserve the immune response and keep people healthy. The knowledge also may be valuable for future diagnostics.

The study is published by the Journal of Biological Chemistry. The paper will appear in its final form in September.

“It’s a battle of supremacy between virus and host,” said Horvath, the senior author of the paper. “Our goal is to understand how the flu replicates in the host. Now we’ve discovered a new pathway in which the flu controls the immune response, by shutting down vital protein production. With better understanding of this mechanism, one day we may be able to customize therapeutics to target individual flu strains.”

Horvath is the Soretta and Henry Shapiro Research Professor in Molecular Biology and professor of molecular biosciences in the Weinberg College of Arts and Sciences. He also is professor of microbiology-immunology and medicine at the Feinberg School of Medicine.

A microRNA has only 17 to 24 nucleotides, and its function is to dampen or shut down the production of proteins in the body. (Proteins are the workhorses of the cell.) There are hundreds of different types of microRNAs in animals.

It’s been known for many years that when a virus such as influenza infects respiratory cells there is an immediate antiviral response at the cellular level — the first barrier for protecting the body from the virus. Most of the changes that occur are a result of antiviral gene expression.

About 10 years ago, scientists first learned about small RNA pathways called microRNAs, which regulate gene expression. This led Horvath to want to investigate the role of microRNAs in influenza virus infection and determine what they are contributing to the antiviral response. Exactly which genes might the microRNAs be targeting?

In their current study, Horvath and his team used human lung cells, infected them with the influenza A virus and looked to see which microRNAs were activated in response to the virus. They focused on six microRNAs that were found to increase in abundance during flu infection.

The researchers found the virus activated two microRNAs that turned on the genes IRAK1 and MAPK3. This resulted in a decrease in the amount of proteins that help turn on the immune response.

Essentially, the virus uses the cell mechanisms to its advantage, disarming parts of the natural antiviral system. The flu takes over the expression of microRNAs for its own purposes. The flu increases the expression of microRNA, which decreases the amount of protein and diminishes the immune response.

Having identified a specific set of microRNAs whose expression in host respiratory cells is changed by the influenza virus, Horvath next is interested at looking at the clinical outcomes. He is working with Pedro C. Avila, M.D., professor of medicine-allergy-immunology at the Feinberg School to see if the microRNAs are disregulated in patients with influenza.

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The title of the paper is “Influenza A Virus Infection of Human Respiratory Cells Induces Primary MicroRNA Expression.” In addition to Horvath, other authors of the paper are first author William A. Buggele and Karen E. Johnson.

Turmeric Spices Up Virus Study – it shows promise in fighting devastating viruses

Posted: August 15, 2012 at 10:47 am, Last Updated: August 15, 2012 at 1:33 pm

By Michele McDonald

Aarthi Narayanan

Aarthi Narayanan. Photo by Evan Cantwell

The popular spice turmeric packs more than just flavor — , Mason researchers recently discovered.

Curcumin, found in turmeric, stopped the potentially deadly Rift Valley Fever virus from multiplying in infected cells, says Aarthi Narayanan, lead investigator on a new study and a research assistant professor in Mason’s National Center for Biodefense and Infectious Diseases.

Mosquito-borne Rift Valley Fever virus (RVF) is an acute, fever-causing virus that affects domestic animals such as cattle, sheep and goats, as well as humans. Results of the study were publishedthis month in the Journal of Biological Chemistry.

“Growing up in India, I was given turmeric all the time,” says Narayanan, who has spent the past 18 months working on the project. “Every time my son has a throat infection, I give (turmeric) to him.”

There’s more work to do before curcumin-based pharmaceuticals become commonplace, Narayanan emphasizes. She plans to test 10 different versions of curcumin to determine which one works the best. She also intends to apply the research to other viruses, including HIV.

Narayanan has long wanted to explore the infection-fighting properties of turmeric, in particular its key component, curcumin. “It is often not taken seriously because it’s a spice,” she says.

But science is transforming the spice from folk medicine to one that could help a patient’s body fight off a virus because it can prevent the virus from taking over healthy cells. These “broad-spectrum inhibitors” work by defeating a wide array of viruses.

Turmeric is often used as a spice in curry dishes. Photo by Sanjay Acharya from Wikipedia Commons

“Curcumin is, by its very nature, broad spectrum,” Narayanan says. “However, in the published article, we provide evidence that curcumin may interfere with how the virus manipulates the human cell to stop the cell from responding to the infection.”

Kylene Kehn-Hall, a co-investigator on the study, adds, “We are very excited about this work, as curcumin not only dramatically inhibits RVFV replication in cell culture but also demonstrates efficacy against RVFV in a mouse model.”

Narayanan and her colleagues study the connection between a virus and how it impacts the host — human or animal. Symptoms clue in the researcher about the body’s inner workings. Rift Valley Fever and Venezuelan Equine Encephalitis kick off with flu-like symptoms.

Symptoms can make it challenging for someone to recover. The body usually starts with an exaggerated inflammatory response because it doesn’t know where to start to rid itself of the virus, she says.

“Many times, the body goes above and beyond what is necessary,” Narayanan says. “And that’s not good because it’s going to influence a bunch of cells around the infection, which haven’t seen the bug. That’s one way by which disease spreads through your body. And so it is very important to control the host because a lot of times the way the host responds contributes to the disease.”

Controlling the symptoms means more than simply making the patients feels better. “You’re giving the antiviral a chance to work. Now an antiviral can go in and stop the bug. You’re no longer trying to keep the host alive and battling the bug at the same time.”

Narayanan works with a graduate student in Mason’s National Center for Biodefense and Infectious Diseases. Photo by Evan Cantwell

Once Narayanan knows how the body responds to a virus, it’s time to go after the bug itself.

She’s applying this know-how to a family of viruses called Bunyaviruses, which feature Rift Valley fever, and such alphaviruses as Venezuelan equine encephalitis and retroviruses, which notably include HIV.

She delves into uncovering why and how each virus affects the patient. “Why are some cell types more susceptible to one type of infection than another?”

HIV goes after the immune system. Bunyaviruses will infect a wide range of cells but do maximum damage to the liver. “What is it about the liver that makes it a sitting duck compared to something like the brain?” Narayanan asks.

Ultimately, curcumin could be part of drug therapies that help defeat these viruses, Narayanan says.

“I know this works. I know it works because I have seen it happen in real life,” Narayanan says. “I eat it every day. I make it a point of adding it to vegetables I cook. Every single day.”

Other Mason researchers involved in the study are Charles Bailey, Ravi Das, Irene Guendel, Lindsay Hall, Fatah Kashanchi, Svetlana Senina and Rachel Van Duyne. Several researchers from other institutions also collaborated.

Write to Michele McDonald  at mmcdon15@gmu.edu

http://newsdesk.gmu.edu/2012/08/turmeric-spices-up-virus-study/

Glucosamine-like supplement suppresses multiple sclerosis attacks

Contact: Tom Vasich tmvasich@uci.edu 949-824-6455 University of California – Irvine

UCI study shows promise of metabolic therapy for autoimmune diseases

Irvine, Calif., Sept. 30, 2011 — A glucosamine-like dietary supplement suppresses the damaging autoimmune response seen in multiple sclerosis, according to a UC Irvine study.

UCI’s Dr. Michael Demetriou, Ani Grigorian and others found that oral N-acetylglucosamine (GlcNAc), which is similar to but more effective than the widely available glucosamine, inhibited the growth and function of abnormal T-cells that in MS incorrectly direct the immune system to attack and break down central nervous system tissue that insulates nerves.

Study results appear online in The Journal of Biological Chemistry.

Earlier this year, Demetriou and colleagues discovered that environmental and inherited risk factors associated with MS – previously poorly understood and not known to be connected – converge to affect how specific sugars are added to proteins regulating the disease.

“This sugar-based supplement corrects a genetic defect that induces cells to attack the body in MS,” said Demetriou, associate professor of neurology and microbiology & molecular genetics, “making metabolic therapy a rational approach that differs significantly from currently available treatments.”

Virtually all proteins on the surface of cells, including immune cells such as T-cells, are modified by complex sugar molecules of variable sizes and composition. Recent studies have linked changes in these sugars to T-cell hyperactivity and autoimmune disease.

In mouse models of MS-like autoimmune disease, Demetriou and his team found that GlcNAc given orally to those with leg weakness suppressed T-cell hyperactivity and autoimmune response by increasing sugar modifications to the T-cell proteins, thereby reversing the progression to paralysis.

The study comes on the heels of others showing the potential of GlcNAc in humans. One reported that eight of 12 children with treatment-resistant autoimmune inflammatory bowel disease improved significantly after two years of GlcNAc therapy. No serious adverse side effects were noted.

“Together, these findings identify metabolic therapy using dietary supplements such as GlcNAc as a possible treatment for autoimmune diseases,” said Demetriou, associate director of UCI’s Multiple Sclerosis Research Center. “Excitement about this strategy stems from the novel mechanism for affecting T-cell function and autoimmunity – the targeting of a molecular defect promoting disease – and its availability and simplicity.”

He cautioned that more human studies are required to assess the full potential of the approach. GlcNAc supplements are available over the counter and differ from commercially popular glucosamine. People who purchase GlcNAc should consult with their doctors before use.

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Lindsey Araujo and Dylan Place of UCI and Nandita N. Naidu and Biswa Choudhury of UC San Diego also participated in the research, which was funded by the National Institutes of Health and the National Multiple Sclerosis Society.

About the University of California, Irvine: Founded in 1965, UCI is a top-ranked university dedicated to research, scholarship and community service. Led by Chancellor Michael Drake since 2005, UCI is among the most dynamic campuses in the University of California system, with nearly 28,000 undergraduate and graduate students, 1,100 faculty and 9,000 staff. Orange County’s largest employer, UCI contributes an annual economic impact of $4.2 billion. For more UCI news, visit www.today.uci.edu.

News Radio: UCI maintains on campus an ISDN line for conducting interviews with its faculty and experts. Use of this line is available for a fee to radio news programs/stations that wish to interview UCI faculty and experts. Use of the ISDN line is subject to availability and approval by the university.

UCI maintains an online directory of faculty available as experts to the media. To access, visit www.today.uci.edu/experts. For UCI breaking news, visit www.zotwire.uci.edu.