(Press-News.org) WASHINGTON D.C. Feb. 19, 2014 -- Proteins are the workhorses of the cell, and their correctly folded three-dimensional structures are critical to cellular functions. Misfolded structures often fail to properly perform these vital jobs, leading to cellular stress and devastating neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease.
In comparison with the mysteries of Alzheimer's or Parkinson's disease, Huntington's disease has a seemingly simple culprit: an expansion in the polyglutamine (polyQ) tract of a protein called "Huntingtin" (Htt). This polyQ expansion causes the Htt protein to misfold, which triggers a cascade of events -- including aggregation of the Htt protein into very stable, fibrillar, amyloid species, and ultimately, neuronal cell death.
"Despite the simplicity of the misfolding involved, we understand very little about why Htt -- an essential protein expressed ubiquitously in all human tissue -- becomes so toxic when misfolded," said Koning Shen, a grad student working in the Frydman Lab at Stanford University.
Shen will describe her team's multipronged efforts to gain a better understanding of the relationship between protein misfolding, aggregation and cell toxicity at the 58th Annual Biophysical Society Meeting, which takes place Feb. 15-19, 2014, in San Francisco, Calif.
The cause of neuronal toxicity in Huntington's disease remains unknown. Until recently, general consensus had associated fibrillar aggregates with pathogenesis in Huntington's disease. Newer studies, however, point to transient, intermediate species called "oligomers," which occur during the aggregation process, as the key players in neurotoxicity, rather than the fibrillar aggregates.
"Identifying the toxic perpetrators will help explain the pathogenesis of not only Huntington's disease, but perhaps Alzheimer's and Parkinson's as well," explained Shen.
Shen and colleagues also hope to discover which molecular factors may contribute to or ameliorate Htt toxicity. An extended polyQ region is the molecular signature of Htt aggregation, but regions flanking the polyQ tract can also alter the aggregation pathway.
"A molecular chaperone called 'TRiC' can suppress Huntington's disease pathogenesis by binding to one of the polyQ-flanking regions. These flanking regions act as a tool to probe the Htt aggregation pathway to learn how Htt forms toxic aggregate species and how the cell has developed tools to stop it," Shen said. "Altering the regions flanking the polyQ tract could remarkably impact both the aggregation and toxicity of the Huntingtin protein."
Deletions or mutations within these regions may either exacerbate or alleviate aggregation -- despite having the same polyQ length. And, Shen pointed out, "fibrillar aggregation and toxicity don't go hand-in-hand amongst these flanking mutants. This finding suggests that there may be toxic intermediate species manifested through the polyQ region, which can be modulated by the polyQ-flanking regions."
Since these flanking region modulations are independent of polyQ length, the ability to use these regions for small molecule or peptide therapeutics delivery will be powerful for Huntington's disease patients, who have already been expressing polyQ-expanded Htt for many years of their lives.
"By manipulating these flanking regions, we may be able to directly influence the aggregation pathway in Huntington's disease patients," said Shen. "Because TRiC binding to a polyQ flanking region suppresses pathogenesis, the interaction between TRiC and Htt shows great potential for therapeutics development."
Recent work has highlighted the ability of a domain of TRiC, called "Apical1," to exhibit TRiC-like effects at suppressing Htt pathogenesis. "This small domain can be more easily adapted into peptide therapeutics and administered to Huntington's disease patients. If developed with an understanding of the toxicity of these misfolded proteins, this next generation of therapeutics may emerge within the next 5 to 10 years," Shen noted.
INFORMATION:
The presentation "Polyglutamine Flanking Regions in Huntingtin Highlight Key Structural Intermediates Relevant for Molecular Chaperone Interaction and Huntington's Disease Pathogenesis"" by Koning Shen, Barbara Calamini, Donald Lo and Judith Frydman will be at 10:30 a.m. on Wednesday, February 19, 2014 in Hall D in San Francisco's Moscone Convention Center.
ABSTRACT: http://tinyurl.com/or3apns
Link to NIH information about Huntington's disease: http://www.ninds.nih.gov/disorders/huntington/huntington.htm
ABOUT THE MEETING
Each year, the Biophysical Society Annual Meeting brings together more than 7,000 researchers working in the multidisciplinary fields representing biophysics. With more than 4,200 poster presentations, over 200 exhibits, and more than 20 symposia, the BPS Annual Meeting is the largest meeting of biophysicists in the world. Despite its size, the meeting retains its small-meeting flavor through its subgroup symposia, platform sessions, social activities, and committee programs.
The 58th Annual Meeting will be held at the Moscone Convention Center, 747 Howard Street, San Francisco, California.
PRESS REGISTRATION
The Biophysical Society invites professional journalists, freelance science writers and public information officers to attend its Annual Meeting free of charge. For press registration, contact Alisha Yocum at ayocum@biophysics.org or Jason Bardi at 240-535-4954.
QUICK LINKS
Main Meeting Page: http://tinyurl.com/mfjh37p
Program Highlights: http://tinyurl.com/mosxrof
Abstracts Search: http://tinyurl.com/lbrearu
ABOUT THE SOCIETY
The Biophysical Society, founded in 1958, is a professional, scientific Society established to encourage development and dissemination of knowledge in biophysics. The Society promotes growth in this expanding field through its annual meeting, monthly journal, and committee and outreach activities. Its 9000 members are located throughout the U.S. and the world, where they teach and conduct research in colleges, universities, laboratories, government agencies, and industry. For more information on the Society, or the 2014 Annual Meeting, visit http://www.biophysics.org
Huntington's disease: Hot on the trail of misfolded proteins' toxic modus operandi
At 58th Biophysical Society Meeting, researchers from Stanford University try to tease out why a lengthened protein leads to Huntington's disease
2014-02-19
ELSE PRESS RELEASES FROM THIS DATE:
Rutgers scientists identify structure of virus that could lead to hepatitis C vaccine
2014-02-19
Rutgers University scientists have determined the structure of a hepatitis C surface protein, a finding that could assist in the development of a vaccine to halt the spread of the the deadly disease that has infected 3.2 million Americans.
Joseph Marcotrigiano, associate professor of chemistry and chemical biology, says this new research – published online today in Nature – describes an outer region of hepatitis C that enables the virus to evade the body's natural immune system response, causing persistent, chronic infection.
Hepatitis C is constantly mutating, allowing ...
The ups and downs of early atmospheric oxygen
2014-02-19
RIVERSIDE, Calif. — A team of biogeochemists at the University of California, Riverside, give us a nontraditional way of thinking about the earliest accumulation of oxygen in the atmosphere, arguably the most important biological event in Earth history.
A general consensus asserts that appreciable oxygen first accumulated in Earth's atmosphere around 2.3 billion years ago during the so-called Great Oxidation Event (GOE). However, a new picture is emerging: Oxygen production by photosynthetic cyanobacteria may have initiated as early as 3 billion years ago, with oxygen ...
NuSTAR telescope takes first peek into core of supernova
2014-02-19
Astronomers for the first time have peered into the heart of an exploding star in the final minutes of its existence.
The feat is one of the primary goals of NASA's NuSTAR mission, launched in June 2012 to measure high-energy X-ray emissions from exploding stars, or supernovae, and black holes, including the massive black hole at the center of our Milky Way Galaxy.
The NuSTAR team reported in this week's issue of the journal Nature the first map of titanium thrown out from the core of a star that exploded in 1671. That explosion produced the beautiful supernova remnant ...
Managed honeybees linked to new diseases in wild bees
2014-02-19
Diseases that are common in managed honeybee colonies are now widespread in the UK's wild bumblebees, according to research published in Nature. The study suggests that some diseases are being driven into wild bumblebee populations from managed honeybees.
Dr Matthias Fürst and Professor Mark Brown from Royal Holloway University of London (who worked in collaboration with Dr Dino McMahon and Professor Robert Paxton at Queen's University Belfast, and Professor Juliet Osborne working at Rothamsted Research and the University of Exeter) say the research provides vital information ...
Gene sequencing project discovers common driver of a childhood brain tumor
2014-02-19
(MEMPHIS, Tenn. – February 19, 2014) The St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project has identified the most common genetic alteration ever reported in the brain tumor ependymoma and evidence that the alteration drives tumor development. The research appears February 19 as an advanced online publication in the scientific journal Nature.
The results provide a foundation for new research to improve diagnosis and treatment of ependymoma, the third most common brain tumor in children. St. Jude has begun work to translate the ...
Managing chronic bone and joint pain
2014-02-19
ROSEMONT, Ill.—Musculoskeletal pain of the bone, joint and muscles is one of the most common reasons for primary care visits in the United States. According to a literature review appearing in a recent issue of the Journal of the American Academy of Orthopaedic Surgeons (JAAOS), chronic pain, or pain that persists beyond an expected period of healing, is estimated to affect 100 million Americans.
The majority of chronic pain complaints concern the musculoskeletal system, but they also include headaches and abdominal pain. "As orthopaedic surgeons, we are experts in the ...
Blood pressure medications given right after stroke not beneficial, study finds
2014-02-19
MAYWOOD, IL – A major study has found that giving stroke patients medications to lower their blood pressure during the first 48 hours after a stroke does not reduce the likelihood of death or major disability.
The study is published in the Journal of the American Medical Association.
At least 25 percent of the population has high blood pressure, which greatly increases the risk of stroke. Lowering blood pressure has been shown to reduce the risk of stroke. The study investigated whether there also would be a benefit to lowering blood pressure immediately after a stroke.
The ...
Reasons for becoming self-employed in later life vary by gender, culture
2014-02-19
COLUMBIA, Mo. – Self-employment can allow older workers to stay in the labor market longer and earn additional income, yet little research has addressed if reasons for self-employment vary across gender and culture. Now, University of Missouri researchers have studied factors that contribute to self-employment and found these factors differ for men and women in the United States and New Zealand.
"Gender is one of the most enduring social factors in the U.S. and New Zealand, a fact that is particularly evident in differing economic opportunities for men and women and their ...
Newly developed chemical restores light perception to blind mice
2014-02-19
Progressive degeneration of photoreceptors—the rods and cones of the eyes—causes blinding diseases such as retinitis pigmentosa and age-related macular degeneration. While there are currently no available treatments to reverse this degeneration, a newly developed compound allows other cells in the eye to act like photoreceptors. As described in a study appearing in the February 19 issue of the Cell Press journal Neuron, the compound may be a potential drug candidate for treating patients suffering from degenerative retinal disorders.
The retina has three layers of nerve ...
Study reveals workings of working memory
2014-02-19
PROVIDENCE, R.I. [Brown University] — Keep this in mind: Scientists say they've learned how your brain plucks information out of working memory when you decide to act.
Say you're a busy mom trying to wrap up a work call now that you've arrived home. While you converse on your Bluetooth headset, one kid begs for an unspecified snack, another asks where his homework project has gone, and just then an urgent e-mail from your boss buzzes the phone in your purse. During the call's last few minutes these urgent requests — snack, homework, boss — wait in your working memory. ...
LAST 30 PRESS RELEASES:
Capturability distinction analysis of continuous and pulsed guidance laws
CHEST expands Bridging Specialties Initiative to include NTM disease and bronchiectasis on World Bronchiectasis Day
Exposure to air pollution may cause heart damage
SwRI, UTSA selected by NASA to test electrolyzer technology aboard parabolic flight
Prebiotics might be a factor in preventing or treating issues caused by low brain GABA
Youngest in class at higher risk of mental health problems
American Heart Association announces new volunteer leaders for 2025-26
Gut microbiota analysis can help catch gestational diabetes
FAU’s Paulina DeVito awarded prestigious NSF Graduate Research Fellowship
Champions for change – Paid time off initiative just made clinical trials participation easier
Fentanyl detection through packaging
Prof. Eran Meshorer elected to EMBO for pioneering work in epigenetics
New 3D glacier visualizations provide insights into a hotter Earth
Creativity across disciplines
Consequences of low Antarctic sea ice
Hear here: How loudness and acoustic cues help us judge where a speaker is facing
A unique method of rare-earth recycling can strengthen the raw material independence of Europe and America
Epilepsy self-management program shows promise to control seizures, improve mood and quality of life
Fat may play an important role in brain metabolism
New study finds no lasting impact of pandemic pet ownership on human well-being
New insights on genetic damage of some chemotherapies could guide future treatments with less harmful side effects
Gut microbes could protect us from toxic ‘forever chemicals’
Novel modelling links sea ice loss to Antarctic ice shelf calving events
Scientists can tell how fast you're aging from a single brain scan
U.S. uterine cancer incidence and mortality rates expected to significantly increase by 2050
Public take the lead in discovery of new exploding star
What are they vaping? Study reveals alarming surge in adolescent vaping of THC, CBD, and synthetic cannabinoids
ECMWF - delivering forecasts over 10 times faster and cutting energy usage by 1000
Brazilian neuroscientist reveals how viral infections transform the brain through microscopic detective work
Turning social fragmentation into action through discovering relatedness
[Press-News.org] Huntington's disease: Hot on the trail of misfolded proteins' toxic modus operandiAt 58th Biophysical Society Meeting, researchers from Stanford University try to tease out why a lengthened protein leads to Huntington's disease