alzheimers

Eighty percent of Labour MPs believe the government should be spending more on dementia research, according to a new poll released today.

The results of the ComRes survey are revealed ahead of a dementia research fringe event being hosted by Alzheimers Society, the Alzheimers Research Trust and Age Concern and Help the Aged at the Labour Party Conference in Brighton today (Monday 28th September).

In a survey of parliamentarians, Labour MPs were found to be more in favour of an increase in investment than either the Liberal Democrats or the Conservatives although all parties showed more than 70 per cent support. The government currently spends £32.4million on dementia research compared to £248.5million on cancer research.

Results from an Alzheimers Research Trust and Alzheimers Society commissioned YouGov poll also revealed today that 59% of Labour voters believe the government should be putting more money into dementia research. The charities will make this call for an increase in funding and for a coordinated approach at the fringe event, Dementia Decade a cure by 2020?.

Broadcaster, journalist and Alzheimers Society Ambassador Fiona Phillips backed the charities call for greater investment and a coordinated plan. She will meet with Prime Minister Gordon Brown and other senior Labour officials at events during the conference. She said

To see the deterioration Alzheimers caused in first my mum and now my dad has been absolutely heart breaking. It is a cruel disease that robs a person of their dignity and places an incredible strain on the lives of their loved ones. We must do everything we can to find a cure. The only way to do this is through research and the only way research can be carried out is if the government provides the necessary investment.

Professor Simon Lovestone from Alzheimers Research Trust, said

Over the next decade we have a good chance of developing new treatments that slow down the rate of progression of Alzheimers disease and other dementias. If we fail to develop new treatments, we are in deep trouble because of the rising costs of caring for dementia in an ageing population. The government needs to increase its support for dementia research and take full advantage of the UKs worldclass scientists in the race for a cure.

Andrew Harrop, Head of Public Policy at Age Concern and Help the Aged said

Dementia is a cruel disease that robs people who are often otherwise fit and healthy of a happy retirement. Around 700,000 people currently live with dementia in the UK with many more friends and family indirectly affected by this heartbreaking disease. This is why Age Concern and Help the Aged is a major funder of dementia research, notably funding the Disconnected Mind research project and why we strongly support calls for more funding for this vital work.

Neil Hunt, Chief Executive of Alzheimers Society who will chair the fringe event, said

Even in the current economic climate there is an appreciation from MPs and the public of the necessity to do everything we can to defeat this devastating condition.

Dementia costs the UK £17billion a year yet the government spend eight times less on dementia research than cancer research. In order to see the same advancements in care and treatment as we have seen for cancer, spending on dementia research needs to be a higher priority. With the right investment and planning dementia can be defeated.

Last week leading author Terry Pratchett spoke of his experience with a rare form of Alzheimers disease and warned of the dangers of a worldwide tsunami of Alzheimers and other dementia diseases unless changes are made.

Startling new statistics on the worldwide prevalence of Alzheimers disease and related dementias are being released today as countries across the globe join together in recognition of World Alzheimers Day.

According to the World Alzheimer Report, released today by Alzheimers Disease International (ADI), an estimated 35.6 million people worldwide will be living with dementia in 2010. This is a 10 per cent increase over previous global dementia prevalence reported in 2005 in The Lancet. According to the new report, dementia prevalence will nearly double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050.

“The information in the 2009 World Alzheimer Report makes it clear that the crisis of dementia cannot be ignored,” says Debbie Benczkowski, Interim CEO of the Alzheimer Society of Canada. “Unchecked, dementia will impose enormous burdens on individuals, families, health care infrastructures, and global economy.”

The report also focuses on the impact of dementia. For example, statistics cited in the new report suggest that 40 to 75 per cent of caregivers have significant psychological illness as a result of their caregiving, and 15 to 32 per cent have depression. Challenges faced by governments and health care systems worldwide are also outlined, and eight global recommendations are offered based on report findings.

This international report is being delivered today amongst a global message of Diagnosing Dementia Seeing it Sooner. The Alzheimer Society is joining Alzheimer organizations across the world, speaking out about the importance of early diagnosis.

“Early diagnosis is an essential first step towards receiving appropriate help and support. Delay in diagnosis means that people with dementia and their caregivers suffer unnecessarily from uncertainty about what is happening, are deprived of the treatment and care they need, and are unable to begin planning for the future,” says Dr. Jack Diamond, Scientific Director of the Alzheimer Society of Canada.

The full 2009 World Alzheimer Report, including the methodology used to prepare it, can be found at alz.co.uk/worldreport.

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Alzheimer Society

The Canadian Institutes of Health Research (CIHR) has announced a grant totaling more than a million dollars for John F. MacDonalds research on Alzheimers disease. MacDonald is the Director of the Robarts Research Institute at The University of Western Ontario.

“If you have a stroke and survive, you have a very high risk of developing Alzheimers disease or another dementia. These diseases are already taking a huge toll on society and costing billions of dollars in health care costs,” says MacDonald. “With the aging population, its a true growth illness.”

The basic problem is how to prevent nerve cells in the brain from dying, and no longer being able to communicate information. The CIHR funding, which totals $1,086,625 over five years, will allow MacDonald to investigate the transmission process between nerve cells. In particular, hes interested in how a unique ion channel, TRPM2, couples with a glutamate receptor called NMDA to assist learning and memory. If this receptor becomes overactivated, for example during a stroke, it produces toxicity which damages or kills the brain cell. MacDonald has developed a peptide which will be tested to see if itll prevent this toxic interaction, without interfering with normal activity.

MacDonald is also one of the coauthors of a Strokerelated study in the September 6th Advance Online Publication of the prestigious journal Nature Neuroscience. Scientists from the University of Toronto, Robarts Research Institute, the Mayo Clinic in Florida, and Kyoto University in Japan identified a way to prevent the death of neurons in the brain by inhibiting the expression of a channel called TRPM7. Michael Tymianski of Toronto was the lead on the study.

MacDonald is collaborating with researchers in Toronto, Japan and Ireland on the CIHR project. Hes also part of an informal network of researchers across Canada dedicated to finding ways to prevent and treat Alzheimers disease. “Finding new types of pharmacological therapy for Alzheimers and related diseases is likely the most important health and social concern for Canada and the developed world.”

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Kathy Wallis

Sticking with what you know often comes at the price of learning about more favorable alternatives.

Managing this tradeoff is easy for many, but not for those with conditions such as Alzheimers disease or obsessivecompulsive disorder who are trapped in simple routines.

Using brain scans in monkeys, Duke University Medical Center researchers are now able to predict when monkeys will switch from exploiting a known resource to exploring their options.

“Humans arent the only animals who wonder if the grass is greener elsewhere, but its hard to abandon what we know in hopes of finding something better,” said John Pearson, Ph.D., research associate in the Duke Department of Neurobiology and lead author of a study published in this weeks Current Biology.

“Studies like this one help reveal how the brain weighs costs and benefits in making that kind of decision,” Pearson said. “We suspect that such a fundamental question engages many areas of the brain, but this is one of the first studies to show how individual neurons can carry signals for these kinds of strategic decisions.”

The researchers looked at how nerve cells fired in a part of the brain known as the posterior cingulate cortex as the monkeys were offered a selection of rewards. Generally, these neurons fired more strongly when monkeys decided to explore new alternatives.

The monkeys started with four rewards to choose from, each a 200 microliter cup of juice. After that, the four targets began to slowly change in value, becoming larger or smaller. The monkeys were free to explore the other targets or stay with the initial target, whose value they knew for certain. Monkeys had to select an option to learn its current value and integrate this information with their knowledge of the chances of getting more juice at a different target.

By studying the individual neurons, the researchers could predict which strategy the monkey would employ.

“These data are interesting from a human health perspective, because the posterior cingulate cortex is the most metabolically active part of the brain when we are daydreaming or thinking to ourselves, and it is also one of the first parts of the brain to show damage in Alzheimers disease,” said Michael Platt, Ph.D., professor of neurobiology and evolutionary anthropology at Duke and senior author of the study.

“People with Alzheimers become set in their ways and dont explore as much, which may be because this part of the brain is damaged,” Platt said. “Likewise, in people with obsessivecompulsive disorder, they can become fixed on certain activities or patterns of activity and cant disengage from them, which may also relate to changes in this part of the brain that renders them mentally unable to switch gears between exploring and exploiting.”

More research is needed to learn about how this part of the brain functions, which might be crucial to the flexible adaptation of strategy in response to changing environments, Pearson said.

Other authors include Benjamin Y. Hayden and Sridhar Raghavachari of the Duke Department of Neurobiology. This work was supported by a National Institute on Drug Abuse postdoctoral fellowship, a National Institutes of Health grant, and the Duke Institute for Brain Studies.

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Mary Jane Gore

With all the hype about beneficial antioxidants in everything from face cream to cereal bars, youd think their targetsoxygen radicalsmust be up to no good. Its true, the buildup of oxygen radicals and other reactive oxygen species (ROS) in cells contributes to aging and possibly to diseases such as cancer and Alzheimers.

But in moderate amounts, ROS also help keep cells healthy by controlling cell division, movement and other normal biological processes.

To better understand the role of ROS in disease, scientists first need to explore how ROS function in healthy cells, and research by a University of Michigan team led by chemical biologist Kate Carroll provides an important new tool for doing that. The research is described in a paper scheduled to be published Sept. 18 in the journal ACS Chemical Biology.

The tool, a small molecule called DAz2, functions something like a subcellular GPS, helping researchers home in on the specific proteins that ROS affect.

The cells of all organisms, from bacteria and yeast to humans, sense ROS through a chemical modification process, known as oxidation, which influences how proteins interact with each other.

“While this overall phenomenon is widely accepted, scientists are still working to identify exactly which proteins are affected by ROS in living cells,” said Carroll, assistant professor of chemistry and a research assistant professor in the Life Sciences Institute. Teasing out which proteins are modified and exactly how and where the modification takes place has been hindered by a lack of tools, but Carrolls group has developed a series of chemical probes for that purpose, of which DAz2 is the latest.

“The new probes allow us to easily sort the proteins we want to analyze and study from other proteins that arent modified by ROS.” Carroll said.

Specifically, DAz2 observes the oxidation of the protein building block cysteine to sulfenic acid, which can control how proteins behave and associate with other proteins. Because the modification of cysteine to sulfenic acid is so transient, it has been difficult to observe, and until recently scientists had identified only a few proteins undergoing this type of oxidation. But using DAz2, which directly detects sulfenic acid in living cells, Carrolls group has identified more than 190 proteins, involved in diverse biological processes, that undergo this modification.

“This tool will allow the investigation of the oxidation of proteins in cellular signaling and many disease states, leading to greater understanding of how these processes operate,” Carroll said. “These findings should pave the way for new therapeutic strategies to combat diseases that involve chronic oxidative stress and should lead to a better overall understanding of how cells work.”

Carrolls coauthors on the paper are graduate student Stephen Leonard and postdoctoral fellow Khalilah Reddie. The researchers received funding from the Life Sciences Institute, the Leukemia & Lymphoma Society and the American Heart Association.

A paper published earlier this year in the journal Chemistry & Biology by Carroll and graduate student Candice Paulsen demonstrated the utility of this class of probes.

Patients infected with a particular subtype of HIV, the virus that causes AIDS, are more likely to develop dementia than patients with other subtypes, a study led by Johns Hopkins researchers shows. The finding, reported in the September Clinical Infectious Diseases, is the first to demonstrate that the specific type of HIV has any effect on cognitive impairment, one of the most common complications of uncontrolled HIV infection.

HIV occurs in multiple forms, distinguished by small differences in the virus genetic sequence and designated by letters A through K. Certain subtypes appear to cluster in particular areas of the world, and others have been associated with different rates of progression to full blown AIDS. Of the 35 million people living worldwide with HIV, the majority live in subSaharan Africa, where subtypes A, C and D dominate.

Nearly half of patients with advanced HIV infections have at least mild cognitive impairments, and about 5 percent have the severe form of cognitive impairment known as dementia.

In earlier research, Ned Sacktor, M.D., and his colleagues found that about 31 percent of patients visiting an infectious disease clinic in the Ugandan capital, Kampala, where subtypes A and D dominate, had dementia. The finding led him and his team to wonder whether patients with different subtypes had different rates of dementia.

Sacktor, professor of neurology at the Johns Hopkins University School of Medicine and a clinician at the Johns Hopkins Bayview Medical Center, and his colleagues studied 60 HIVinfected patients from a Kampala clinic. All of the subjects had been part of a different study testing the effect of antiretroviral drugs on cognitive impairment, but had not begun taking the drugs. After determining each patients HIV subtype, they performed a battery of neurological and cognitive tests to assess each patients brain function.

As expected, the majority of the patients had HIV subtypes A or D. Out of the 33 subtype A patients, the researchers determined that seven had dementia, or about 24 percent. However, out of the nine patients with subtype D, 8 had dementia, about 89 percent.

“We were amazed to see such a dramatic difference in dementia frequencies between these two subtypes,” Sacktor says. “If this is the case in all of subSaharan Africa, HIVassociated dementia may be one of the most common, but thus far unrecognized, dementias worldwide.”

The research suggests that some biological property of each subtype seems to influence the likelihood that infected patients will develop dementia, says Sacktor. He and his team hypothesize that subtype D may cause more inflammation and injury in the brain, a possibility they are currently investigating.

A 65yearold women goes into the hospital for routine hip surgery. Six months later, she develops memory loss and is later diagnosed with Alzheimers Disease. Just a coincidence? Researchers at the University of South Florida and Vanderbilt University dont think so. They suspect that the culprit precipitating Alzheimers disease in the elderly women may be a routine administration of high concentrations of oxygen for several hours during, or following, surgery a hypothesis borne out in a recent animal model study.

Dr. Gary Arendash of the Florida Alzheimers Disease Research Center at USF and Dr. L. Jackson Roberts II at Vanderbilt University used mice genetically altered to develop abnormal levels of the protein beta amyloid, which deposits in the brain as plaques and eventually leads to Alzheimerslike memory loss as the mice age. They found that young adult Alzheimers mice exposed to 100percent oxygen during several 3hour sessions demonstrated substantial memory loss not otherwise present at their age. Young adult Alzheimers mice exposed to normal air had no measurable memory loss, and neither did normal mice without any genetic predisposition for Alzheimers disease.

The authors suggest that people genetically predisposed to Alzheimers disease or with excessive amounts of beta amyloid in their brains are at increased risk of developing the disease earlier if they receive high concentrations of oxygen, known as hyperoxia. Their study is published online this month in NeuroReport.

“Although oxygen treatment beneficially increases the oxygen content of blood during or after major surgery, it also has several negative effects that we believe may trigger Alzheimers symptoms in those destined to develop the disease,” said USF neuroscientist Arendash, the studys lead author. “Our study suggests that the combination of brain beta amyloid and exposure to high concentrations of oxygen provides a perfect storm for speeding up the onset of memory loss associated with Alzheimers Disease.”

While postoperative confusion and memory problems are common and usually transient in elderly patients following surgery, some patients develop permanent Alzheimerslike cognitive impairment that remains unexplained. Recent studies have indicated that general anesthesia administered during surgery may increase a patients risk of Alzheimers disease, but the laboratory studies did not use animals or people predisposed to develop the disease.

“Postoperative memory loss can be a fairly common and devastatingly irreversible problem in the elderly after major surgical procedures,” said Roberts, an MD who holds an endowed chair in Pharmacology at Vanderbilt University School of Medicine. “There has been much speculation as to the cause of this memory loss, but the bottom line is that no one really knows why it happens. If all it takes to prevent this is reducing the exposure of patients to unnecessarily high concentrations of oxygen in the operating room, this would be a major contribution to geriatric medicine.”

The USFVanderbilt study looked at 11 young adult mice genetically modified to develop memory problems as they aged, mimicking Alzheimers disease. After behavioral tests confirmed the mice had not yet developed memory impairment at age 3 months about age 40 in human years the researchers exposed half the Alzheimers mice to 100percent oxygen for three hours, three times over the next several months. The protocol was intended to replicate initial and supplemental exposures of elderly patients in hospital operating rooms and recovery suites to high concentrations of oxygen. The other half of the mice were exposed to 21percent oxygen, the concentration of oxygen in typical room air.

When researchers retested the mice after the final gas exposure, they found that Alzheimers mice exposed to 100percent oxygen performed much worse on tests measuring their memory and thinking skills than the Alzheimers mice exposed to normal room air. In fact, the Alzheimers mice exposed to room air demonstrated no memory loss. Moreover, exposure of young adult mice without beta amyloid protein deposited in their brains to 100percent oxygen did not adversely affect their memories. This is consistent with studies in humans showing that exposure of young adults to high concentrations of oxygen has no harmful effects on memory.

The researchers also demonstrated that even a single 3hour exposure to 100percent oxygen caused memory deficits in the Alzheimers mice. Furthermore, when they examined the brains of these mice, they found dramatic increases in levels of isofurans, products of oxygeninduced damage from toxic free radicals. The increase was not present in the brains of normal control mice exposed to the single hyperoxia treatment.

How might high concentrations of oxygen hasten memory impairment in those destined to develop Alzheimers disease? The researchers suggest the striking increase of isofurans during surgery may be one triggering mechanism, particularly in cardiac bypass surgery where very high blood oxygen levels are routinely attained and permanent memory loss often occurs months after the surgery. Secondly, exposure to high concentrations of oxygen prompts abnormal swelling of brain cell terminals that transmit chemical messages from one brain cell to another and may further disrupt already frayed nerve cell connections in those at risk for Alzheimers. Third, high concentrations of oxygen combined with beta amyloid plaques constricts blood vessels and decreases blood flow to the brain more than either one alone.

The authors caution that the study in mice may or may not accurately reflect the effects of hyperoxia in human surgery patients.

“Nonetheless, our results call into question the wide use of unnecessarily high concentrations of oxygen during and/or following major surgery in the elderly,” Roberts said. “These oxygen concentrations often far exceed that required to maintain normal hemoglobin saturation in elderly patients undergoing surgery.”

Notes
Arendash published initial evidence in 1987 that Alzheimers disease starts in the brain several decades before memory loss occurs. His research focuses on developing promising therapeutics in Alzheimers mice that can quickly be transferred to human clinical trials. Roberts, an expert on the role of free radicals and oxidative injury in disease, has discovered novel products of free radical damage that may be associated with several agerelated brain dysfunctions. Also participating in the hyperoxia study were Dr. Takashi Mori of Saitama Medical University (Japan) and Dr. Kenneth Hensley of the Oklahoma Medical Research Foundation. The study was supported by grants within the Florida Alzheimers Disease Research Center, a statewide project sponsored by the National Institute on Aging, and a National Institutes of Health Merit Award to Dr. Roberts.
An estimated 10 million baby boomers will develop Alzheimers disease in their lifetime. The disease usually begins after age 60, and risk rises with aging. The direct and indirect cost of Alzheimers disease in the United States is a staggering $150 billion a year, according to the national Alzheimers Association.

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Gary Arendash, PhD

UCLA scientists have discovered a way to measure the amount of amyloid beta that is being absorbed by immune cells in the blood. Amyloid beta forms the plaques considered the hallmark of Alzheimers disease, and if the immune system isnt adequately clearing amyloid beta, it may indicate Alzheimers risk, according to the researchers.

MP Biomedicals LLC, a global life sciences and diagnostics company dedicated to Alzheimers disease research, has received an exclusive, worldwide license to commercialize the UCLA technology and create a diagnostic blood test for public use to screen for Alzheimers risk.

“Early diagnosis is the cornerstone of preventive approaches to Alzheimers disease,” said Dr. Milan Fiala, lead author of the UCLA study and a researcher at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System. “We are pleased that the process weve identified using immune cells to help predict Alzheimers risk will be further developed by MP Biomedicals.”

“We are excited by the opportunity to forward the UCLA science in creating a costeffective blood test to screen for Alzheimers risk that could be used in any hospital or lab,” said Milan Panic, CEO of MP Biomedicals.

Dr. Miodrag Micic, vice president of research and development for MP Biomedicals, noted that other blood tests for Alzheimers diagnosis measure factors such as inflammation and infection, which are also present in other diseases like atherosclerosis and may complicate the interpretation of results.

The recently published study on the process identified by UCLA, which uses the “innate” immune system present at birth, appeared in the May issue of the Journal of Neuroimmunology.

In the study, researchers took blood samples and isolated monocytes, which from birth act as the immune systems janitors, traveling through the brain and body and gobbling up waste products including amyloid beta. The monocytes were incubated overnight with amyloid beta, which was labeled with a fluorescent marker. Using a common laboratory method known as flow cytometry, researchers then measured the amount of amyloid beta ingested by the immune cells by assessing how much fluorescence was being emitted from each monocyte cell.

The 18 Alzheimers disease patients in the study showed the least uptake of amyloid beta; the healthy control group, which consisted of 14 university professors, demonstrated the highest uptake. The method was able to distinguish with adequate sensitivity and specificity the Alzheimers disease patients.

The results were found to be positive in 94 percent of the Alzheimers patients and negative in 100 percent of the university professor control group. In addition, the results were found to be positive in 60 percent of study participants who suffered from mild cognitive impairment, a condition that increases the risk of developing Alzheimers.

“Patients and control subjects were also tracked over time to see if their immune response changed,” Fiala said. For example, an Alzheimers disease patient over time showed declining results, while a university professor continued to demonstrate a high uptake of amyloid beta.

Micic noted that the new method could be a flag for further testing and interventions.

“Similar to screening patients for heart disease risk by a cholesterol test, a positive result for Alzheimers risk in some patients may suggest further interventions and advanced diagnostics, such as a brain PET scan and neurocognitive testing.”

The study was funded in part by MP Biomedicals LLC. Fiala is a consultant for the company and also served in the companys speakers bureau.

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The David Geffen School of Medicine at UCLA

A major research grant will help scientists study the links between memory and oral health in a bid to establish control over Alzheimers disease.The news of a $1.3 million study to be carried out on thousands of participants has been welcomed by the UKs leading oral health charity the British Dental Health Foundation.

Research has long associated oral health with overall health problems, including dementia though no studies have made clear how the state of the teeth and mouth affect mental function.

Last year researchers found a link between mild memory loss and gum disease* and the sevenfigure grant will enable examination of medical records of thousands of Americans to further pursue the link.

Foundation chief executive Dr Nigel Carter welcomed the news saying “Oral health and gum disease in particular has been increasingly linked to overall health through studies such as this exciting piece of research.

“The recent review of NHS dentistry suggested the government is committed to preventive care.

“It would be a great boost if scientists could prove preventive treatment could not only protect our teeth but also help prevent chronic diseases such as Alzheimers.”We will watch developments with interest and urge the public to make sure they look after their oral health with simple steps which can reduce the risk of gum disease.”Minimising the risks caused by poor oral hygiene is as simple as brushing teeth twice a day with a fluoride toothpaste and visiting the dentist regularly for professional checkups.”

The US studies will be led by Dr Bei Wu of the University of North Carolina and Dr Richard Crout of the University of West Virginia, who will continue with a program testing oral health and memory in 273 people aged 70.

The new funding will establish larger studies looking for links between oral health and brain function over time, while scientists will also seek to establish a link between improved cognitive function and better oral hygiene through intervention to improve oral health.

In an interview this week Dr Crout, who has predicted that dentists may in future be in a position to administer memory tests on older patients, said “to have overall good general health you need to have good oral health.”

Johns Hopkins researchers have discovered a novel protein that can protect brain cells by interrupting a naturally occurring “stress cascade” resulting in cell death.

Reporting in the July 16 issue of the journal Neuron, the scientists say drugs mimicking the protein, nicknamed GOSPEL, have the potential to protect brain cells against a range of neurodegenerative conditions, including stroke and Alzheimers and Huntingtons diseases.

“This work has potentially broad clinical implications,” says senior author Akira Sawa, M.D., Ph.D., director of molecular psychiatry.

Sawa and his team, in collaboration with Johns Hopkins neuroscientist Solomon Snyder, M.D., and his team, conducted experiments showing that GOSPEL competes with a second protein when it tries to latch on to glyceraldehyde3phosphate dehydrogenase or GAPDH, a multifunctional molecule. By binding to GAPDH itself, GOSPEL both prevents the cell death cascade and offers brain cells protection against potentially toxic agents.

Sawa has spent more than a decade studying GADPH activity and its role in socalled oxidativestressinduced cellular responses, including programmed cell death.

That cascading process begins when various stressors such as injury or disease activate a complex enzyme, nitric oxide synthase, which then forms nitric oxide, a chemical that transmits signals between nerves but also is toxic to cells. Excess levels of nitric oxide cause GAPDH to undergo a chemical modification called Snitrosylation that in turn lets it bind to another protein called Siah1. The combined GAPDHSiah1 molecules then move into a cells nucleus, hijack key portions of its DNA and set off a chain of reactions leading to cell death.

In the currently reported study, the researchers analyzed tissue samples from rats to identify the DNA coding for GOSPEL (which stands for GAPDHs competitor Of Siah Protein Enhances Life) and found that the protein exists in tissues in the brain, heart, lung and skeletal muscle, though it is most widely expressed in neurons in the central nervous system.

A series of laboratory experiments in mouse brain tissue found that Snitrosylation is necessary to enable GOSPEL to bind to GAPDH; that GOSPEL competes with Siah for GAPDH binding; that GOSPEL prevents GAPDH from slipping into the cell nucleus; and that GOSPEL diminishes brain cell damage by preventing the binding of GAPDH and Siah.

To determine whether GOSPELs neuroprotective actions were evident in live mice, the scientists used a benign virus to deliver either GOSPEL or an altered version of GOSPEL lacking the property to bind with GAPDH into the animals brains. They then injected a neurotransmitter, NMDA, to induce and simulate other kinds of brain damage. The researchers found that NMDAinduced lesions in the brains of mice injected with GOSPEL were about 30 percent smaller than in those injected with the altered GOSPEL, showing that the neuroprotective influence of GOSPEL related to its ability to bind to GAPDH.

The GOSPEL molecule was first available in the database of the Human Genome Project, Sawa says, but until now was designated as a genetic compound with no known properties.

The work was supported by grants from the U.S. Public Health Service, the Stanley Medical Research Institute, NARSAD (the National Alliance for Research on Schizophrenia and Depression), the CHDI Foundation, and the SR Foundation.

Coauthors were Nilkantha Sen, Makoto R. Hara, Abdullah Shafique Ahmed, Matthew B. Cascio, Atsushi Kamiya, Jeffrey T. Ehmsen, Nishant Aggrawal, Lynda Hester, Sylvain Dore, and Solomon H. Snyder, M.D.

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