February 17, 2011, 7:05 AM CT
Increasing brain enzyme may slow Alzheimer's disease
Stanislav Karsten, an LA BioMed principal researcher, is the lead author of a new study on Alzheimer's disease.
Credit: LA BioMed
Increasing puromycin-sensitive aminopeptidase, the most abundant brain peptidase in mammals, slowed the damaging accumulation of tau proteins that are toxic to nerve cells and eventually lead to the neurofibrillary tangles, a major pathological hallmark of Alzheimer's disease and other forms of dementia, as per a research studypublished online in the journal,
Human Molecular GeneticsScientists found they could safely increase the puromycin-sensitive aminopeptidase, PSA/NPEPPS, by two to three times the usual amount in animal models, and it removed the tau proteins in the neurons. Removing the tau proteins restored neuronal density and slowed down disease progression. Scientists detected no abnormalities caused by the increase in PSA/NPEPPS, suggesting that elevating PSA/NPEPPS activity appears to be a viable approach to treat Alzheimer's disease and other forms of dementia, known a tauopathies.
"Our research demonstrated that increasing the brain enzyme known as PSA/NPEPPS can effectively block the accumulation of tau protein that is toxic to nerve cells and slow down the progression of neural degeneration without unwanted side effects," said Stanislav L. Karsten, PhD, the corresponding author for the study and a principal investigator at Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed). "These findings suggest that increasing this naturally occurring brain peptidase, PSA/NPEPPS, appears to be a feasible therapeutic approach to eliminate the accumulation of unwanted toxic proteins, such as tau, that cause the neural degeneration linked to the devastating effects of Alzheimer's disease and other forms of dementia".........
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February 17, 2011, 7:00 AM CT
Tau-induced memory loss in Alzheimer's mice
To test their capacity to learn, the mice are trained to find an underwater platform which is not visible to them from the edge of a water basin. The swimming path is marked in red. Normal mice learn to find the path after just a few training sessions; they remember it and swim straight to the platform (left) when tested. A mouse with too much aggregated tau protein in its neurons finds it difficult to learn and swims aimlessly around the basin (centre) for extended periods. If the gene for the toxic tau protein in this mouse is switched off for a few weeks using a genetic trick, the mouse is able to learn normally again and quickly finds its way to the platform (right). © Max-Planck-ASMB/Mandelkow
Amyloid-beta and tau protein deposits in the brain are characteristic features of Alzheimer disease. The effect on the hippocampus, the area of the brain that plays a central role in learning and memory, is especially severe. However, it appears that the toxic effect of tau protein is largely eliminated when the corresponding tau gene is switched off. Scientists from the Max Planck Research Unit for Structural Molecular Biology at DESY in Hamburg have succeeded in demonstrating that once the gene is deactivated, mice with a human tau gene, which previously presented symptoms of dementia, regain their ability to learn and remember, and that the synapses of the mice also reappear in part. The researchers are now testing active substances to prevent the formation of tau deposits in mice. This may help to reverse memory loss in the early stages of Alzheimer disease - in part, at least.
Whereas aggregated amyloid-beta protein forms insoluble clumps between the neurons, the tau protein accumulates inside them. Tau protein stabilises the tube-shaped fibers of the cytoskeleton, known as microtubules, which provide the "rails" for cellular transport. In Alzheimer disease, excess phosphate groups cause the tau protein to malfunction and form clumps (the 'neurofibrillary tangles'). As a result, nutrient transport breaks down and the neurons and their synapses die off. This process is accompanied by the initial stage of memory loss.........
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February 17, 2011, 6:54 AM CT
Healthy lifestyle, positive attitude
Joint replacement patients who improve their lifestyle and maintain a positive mindset previous to surgery are more likely to have better functional outcomes than those who do not, as per research presented today at the 2011 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS). Multiple studies observed that patients who smoke, misuse alcohol, fail to control blood sugar levels or simply have a poor attitude previous to undergoing total hip or knee replacement (THR/TKR) surgery can, in some cases, double their odds of post-operative complications.
Data were presented in three separate studies and one instructional course by scientists from Stanford University, the University of Alabama, the Orthopedic Institute in Miami and the University of Massachusetts.
"Some known risk factors for complications like advanced age and pre-existing heart or lung conditions are difficult or impossible to modify previous to surgery," said Jasvinder Singh, MD, associate professor of medicine at the University of Alabama in Birmingham. "In contrast, smoking, alcohol abuse, blood sugar levels and mental attitude are completely manageable by the patients themselves, which makes them an excellent target for prevention and intervention programs that are likely to improve outcomes".........
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February 14, 2011, 7:39 AM CT
Reduced levels of neurotransmitter in MS
Scientists at the University of Illinois at Chicago have demonstrated for the first time that damage to a particular area of the brain and a consequent reduction in noradrenaline are linked to multiple sclerosis.
The study is available online in the journal
BrainThe pathological processes in MS are not well understood, but an important contributor to its progression is the infiltration of white blood cells involved in immune defense through the blood-brain barrier.
Douglas Feinstein, research professor in anesthesiology at the UIC College of Medicine, and colleagues previously showed that the neurotransmitter noradrenaline plays an important role as an immunosuppressant in the brain, preventing inflammation and stress to neurons. Noradrenaline is also known to help to preserve the integrity of the blood-brain barrier.
Because the major source of noradrenaline is neurons in an area of the brain called the locus coeruleus, the UIC scientists hypothesized that damage to the LC was responsible for lowered levels of noradrenaline in the brains of MS patients.
"There's a lot of evidence of damage to the LC in Alzheimer's and Parkinson's disease, but this is the first time that it has been demonstrated that there is stress involved to the neurons in the LC of MS patients, and that there is a reduction in brain noradrenaline levels," said Paul Polak, research specialist in the health sciences in anesthesiology and first author on the paper.........
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February 14, 2011, 7:37 AM CT
Blood test to detect Alzheimer's disease
UT Southwestern Medical Center researchers have helped develop a novel technology to diagnose Alzheimer's disease from blood samples long before symptoms appear.
This preliminary technology, which uses synthetic molecules to seek out and identify disease-specific antibodies, also could be used eventually in the development of specific biomarkers for a range of other hard-to-diagnose diseases and conditions, including Parkinson's disease and immune system-related diseases like multiple sclerosis and lupus, the scientists predict.
"One of the great challenges in treating patients with Alzheimer's disease is that once symptoms appear, it's too late. You can't un-ring the bell," said Dr. Dwight German, professor of psychiatry and an author of the paper reported in the Jan. 7 edition of
Cell "If we can find a way to detect the disease in its earliest stages � before cognitive impairment begins � we might be able to stop it in its tracks by developing new therapy strategies".
Because patients with Alzheimer's disease (AD) exhibit immune system activation and neurodegeneration in several brain regions, scientists in the study hypothesized that there appears to be numerous antibodies in the serum of affected patients that are specific to the disease and can serve as a biomarker.........
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February 14, 2011, 7:35 AM CT
Compound blocks brain cell destruction in Parkinson's disease
Researchers from the Florida campus of The Scripps Research Institute have produced the first known compound to show significant effectiveness in protecting brain cells directly affected by Parkinson's disease, a progressive and fatal neurodegenerative disorder.
Eventhough the findings were in animal models of the disease, the effectiveness of the compound, combined with its potential to be taken orally, offers the tantalizing possibility of a potentially useful future treatment for Parkinson's disease patients.
The results were published in two separate studies in the journal
ACS Chemical Neuroscience"These studies present compelling data on the first oral, brain-penetrating inhibitor to show significant efficacy in preventing neurodegeneration in both mouse and rat models of Parkinson's disease," said team leader Philip LoGrasso, a professor in the Department of Molecular Therapeutics and senior director for drug discovery at Scripps Florida. "The compound offers one of the best opportunities we have for the development of an effective neuroprotective therapy".
The new small molecule�labeled SR-3306�is aimed at inhibiting a class of enzymes called c-jun-N-terminal kinases (JNK). Pronounced "junk," these enzymes have been shown to play an important role in neuron (nerve cell) survival. As such, they have become a highly viable target for drugs to treat neurodegenerative disorders such as Parkinson's disease.........
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February 14, 2011, 7:33 AM CT
Circulating Tumor Cell Detection
Gold-based nanoparticles can detect circulating tumor cells.
Tiny gold particles can help doctors detect tumor cells circulating in the blood of patients with head and neck cancer, scientists at Emory and Georgia Tech have found.
The detection of circulating tumor cells (CTCs) is an emerging technique that can allow oncologists to monitor patients with cancer for metastasis or to evaluate the progress of their therapy. The gold particles, which are embedded with dyes allowing their detection by laser spectroscopy, could enhance this technique's specificity by reducing the number of false positives.
The results are published online in the journal Cancer Research.
One challenge with detecting CTCs is separating out signals from white blood cells, which are similarly sized as tumor cells and can stick to the same antibodies normally used to identify tumor cells. Commercially available devices trap CTCs using antibody-coated magnetic beads, and technicians must stain the trapped cells with several antibodies to avoid falsely identifying white blood cells as tumor cells.
Emory and Georgia Tech scientists show that polymer-coated and dye-studded gold particles, directly associated with a growth factor peptide rather than an antibody, can detect circulating tumor cells in the blood of patients with head and neck cancer.........
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February 14, 2011, 7:16 AM CT
Children with ADHD and substance abuse
Children with attention-deficit hyperactivity disorder are two to three times more likely than children without the disorder to develop serious substance abuse problems in adolescence and adulthood, as per a research studyby UCLA psychology experts and his colleagues at the University of South Carolina.
"This greater risk for children with ADHD applies to boys and girls, it applies across race and ethnicity � the findings were very consistent," said Steve S. Lee, a UCLA assistant professor of psychology and main author of the study. "The greater risk for developing significant substance problems in adolescence and adulthood applies across substances, including nicotine, alcohol, marijuana, cocaine and other drugs." .
Lee and colleagues analyzed 27 long-term studies that followed approximately 4,100 children with ADHD and 6,800 children without the disorder into adolescence and young adulthood � in some cases for more than 10 years. These carefully designed, rigorous and lengthy studies, Lee said, are the "gold standard" in the field.
The research by Lee and colleagues, the first large-scale comprehensive analysis on this issue, is published online this week in the journal
Clinical Psychology Review and will appear in a print edition later this year.........
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February 14, 2011, 7:07 AM CT
Flavonoids may lower risk of Parkinson's
New research shows men and women who regularly eat berries may have a lower risk of developing Parkinson's disease, while men may also further lower their risk by regularly eating apples, oranges and other sources rich in dietary components called flavonoids. The study was released recently and will be presented at the American Academy of Neurology's 63rd Annual Meeting in Honolulu April 9 to April 16, 2011.
Flavonoids are found in plants and fruits and are also known collectively as vitamin P and citrin. They can also be found in berry fruits, chocolate, and citrus fruits such as grapefruit.
The study involved 49,281 men and 80,336 women. Scientists gave participants questionnaires and used a database to calculate intake amount of flavonoids. They then analyzed the association between flavonoid intakes and risk of developing Parkinson's disease. They also analyzed consumption of five major sources of foods rich in flavonoids: tea, berries, apples, red wine and oranges or orange juice. The participants were followed for 20 to 22 years.
During that time, 805 people developed Parkinson's disease. In men, the top 20 percent who consumed the most flavonoids were about 40 percent less likely to develop Parkinson's disease than the bottom 20 percent of male participants who consumed the least amount of flavonoids. In women, there was no relationship between overall flavonoid consumption and developing Parkinson's disease. However, when sub-classes of flavonoids were examined, regular consumption of anthocyanins, which are mainly obtained from berries, were found to be linked to a lower risk of Parkinson's disease in both men and women.........
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February 14, 2011, 6:59 AM CT
Gonorrhea acquires a piece of human DNA
If a human cell and a bacterial cell met at a speed-dating event, they would never be expected to exchange phone numbers, much less genetic material. In more scientific terms, a direct transfer of DNA has never been recorded from humans to bacteria.
Until now. Northwestern Medicine scientists have discovered the first evidence of a human DNA fragment in a bacterial genome � in this case,
Neisseria gonorrhoeae, the bacterium that causes gonorrhea. Further research showed the gene transfer may be a recent evolutionary event.
The discovery offers insight into evolution as well as gonorrhea's nimble ability to continually adapt and survive in its human hosts. Gonorrhea, which is transmitted through sexual contact, is one of the oldest recorded diseases and one of a few exclusive to humans.
"This has evolutionary significance because it shows you can take broad evolutionary steps when you're able to acquire these pieces of DNA," said study senior author Hank Seifert, professor of microbiology and immunology at Northwestern University Feinberg School of Medicine. "The bacterium is getting a genetic sequence from the very host it's infecting. That could have far reaching implications as far as how the bacteria can adapt to the host".
It's known that gene transfer occurs between different bacteria and even between bacteria and yeast cells. "But human DNA to a bacterium is a very large jump," said main author Mark Anderson, a postdoctoral fellow in microbiology. "This bacterium had to overcome several obstacles in order to acquire this DNA sequence".........
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