(Press-News.org) (MEMPHIS, Tenn. – August 28, 2013) Researchers have tied mutations in a gene that causes amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders to the toxic buildup of certain proteins and related molecules in cells, including neurons. The research, published recently in the scientific journal Cell, offers a new approach for developing treatments against these devastating diseases.
Scientists at St. Jude Children's Research Hospital and the University of Colorado, Boulder, led the work.
The findings provide the first evidence that a gene named VCP plays a role in the break-up and clearance of protein and RNA molecules that accumulate in temporary structures called RNA granules. RNAs perform a variety of vital cell functions, including protein production. RNA granules support proper functioning of RNA.
In ALS and related degenerative diseases, the process of assembling and clearing RNA granules is impaired. The proteins and RNAs associated with the granules often build up in nerve cells of patients. This study shows how mutations in VCP might contribute to that process and neurodegenerative disease.
"The results go a long way to explaining the process that links a variety of neurodegenerative diseases, including ALS, frontotemporal dementia and related diseases of the brain, muscle and bone known as multisystem proteinopathies," said the study's co-corresponding author, J. Paul Taylor, M.D., Ph.D., a member of the St. Jude Department of Developmental Neurobiology. Roy Parker, Ph.D., of the University of Colorado's Department of Chemistry and Biochemistry and the Howard Hughes Medical Institute (HHMI), is the other corresponding author.
ALS, also known as Lou Gehrig's disease, is diagnosed in about 5,600 Americans annually and is associated with progressive deterioration of nerve cells in the brain and spine that govern movement, including breathing. There is no effective treatment, and death usually occurs within five years.
"A strength of this study is that it provides a unifying hypothesis about how different genetic mutations all affect stress granules, which suggests that understanding stress granule dynamics and how they can be manipulated might be beneficial for treatment of these diseases," Parker said.
Earlier work from Taylor's laboratory identified mutations in VCP as a cause of ALS and related multisystem proteinopathies. Until now, however, little was known about how those mistakes caused disease. The latest findings appeared in the June 20 issue and are highlighted in a review article published in the August 15 issue of Cell.
The research also ties VCP mutations to disruption of RNA regulation, which prior studies have connected to the progression of neurodegenerative diseases, said Regina-Maria Kolaitis, Ph.D., a postdoctoral fellow in Taylor's laboratory. She and Ross Buchan, Ph.D., a postdoctoral fellow in Parker's laboratory, are co-first authors.
The work focused on a class of RNA granules called stress granules. They are formed by proteins and an RNA molecule called mRNA that accumulates in the cell cytoplasm in response to stress. Stressed cells do not want to waste energy producing unnecessary proteins. Stress granules are one mechanism cells use to halt production until the cellular environment normalizes, which is when stress granules typically dissolve.
Proteins found in stress granules include RNA-binding proteins like TDP-43, FUS, hnRNPA1 and hnRNPA2B1 that regulate gene activity. Mutations in those proteins can also cause ALS and related disorders.
"VCP has many functions in cells, but it is not an RNA-binding protein and until now it was not connected to stress granules or RNA processing," Kolaitis said. "This study provides a new window into the disease process, highlighting VCP's role in keeping cells healthy."
For this study, researchers used yeast to identify a network of 125 genes that affect the formation and behavior of stress granules. One of the genes that appeared to play a central role in the network was CDC48, which functions like VCP in yeast. In addition, many of the genes identified are involved in a process called autophagy that cells use to break down and recycle unneeded molecules, including proteins.
Working in yeast and mammalian cells, researchers showed that stress granules are cleared by autophagy, which stalled when VCP was mutated. Researchers also reported that stress granules accumulated following mutation of either CDC48 or VCP.
"This work suggests that activating autophagy to help rid cells of stress granules offers a new approach to neurodegenerative disease treatment," Taylor said.
###
The research was supported part by the ALS Association, the Packard Center for ALS Research, the HHMI and ALSAC.
St. Jude Media Relations Contacts
Summer Freeman
(desk) (901) 595-3061
(cell) (901) 297-9861
summer.freeman@stjude.org
Carrie Strehlau
(desk) (901) 595-2295
(cell) (901) 297-9875
carrie.strehlau@stjude.org
St. Jude Children's Research Hospital scientists identify ALS disease mechanism
Study strengthens link between amyotrophic lateral sclerosis and problems in protein production machinery of cells and identifies possible treatment strategy
2013-08-28
ELSE PRESS RELEASES FROM THIS DATE:
GSA Today science: Biofilms, MISS, and stromatolites
2013-08-28
Boulder, Colorado, USA – In the September issue of GSA Today, Nora Noffke of Old Dominion University and Stan Awramik of the University of California, Santa Barbara, describe the interaction of carpet-like communities of benthic microorganisms (biofilms) with sediment dynamics at the sediment-water interface to form distinctive sedimentary structures called microbialites.
The best known microbialite structures are stromatolites -- multilayered microbialites up to meters in thickness, built up by repetitive binding, biostabilization, baffling, and trapping of sediment ...
Autistic children can outgrow difficulty understanding visual cues and sounds
2013-08-28
VIDEO:
Dr. John Foxe has shown that high-functioning autism spectrum disorder (ASD) children appear to outgrow a critical social communication disability. The paper was published online August 28, 2013, in Cerebral...
Click here for more information.
BRONX, NY -- Scientists at Albert Einstein College of Medicine of Yeshiva University have shown that high-functioning autism spectrum disorder (ASD) children appear to outgrow a critical social communication disability. Younger children ...
Dementia sufferers more likely to be diagnosed with urinary or fecal incontinence
2013-08-28
Patients with a diagnosis of dementia have approximately three times the rate of diagnosis of urinary incontinence, and more than four times the rate of fecal incontinence, compared with those without a diagnosis of dementia, according to a study in this week's issue of PLOS Medicine by Robert Grant (Kingston University and St. George's, University of London) and colleagues. Furthermore, patients with dementia and incontinence were more likely to receive incontinence medications and indwelling catheters than those with incontinence but without dementia, the authors state. ...
The importance of treating pediatric AIDS in the elimination agenda
2013-08-28
Scott Kellerman and colleagues argue that the scope of the current HIV elimination agenda must be broadened in order to ensure access to care and treatment for all children living with HIV.
In 2011, despite the global initiative to eliminate mother-to-child transmission of HIV, 330,000 new pediatric infections were added worldwide to the existing pool of 3.4 million children living with the virus. Children are more vulnerable to HIV infection and have higher morbidity and mortality. Without treatment, half of those children infected will die before the age of 2 years, ...
T-cell targeted therapy tested in type 1 diabetes study
2013-08-28
WA, Seattle (August 28, 2013) – Results from the START clinical study (Study of Thymoglobulin to Arrest Newly Diagnosed Type 1 Diabetes), led by Dr. Steve Gitelman (University of California, San Francisco) and sponsored by the Immune Tolerance Network (ITN), are published today in The Lancet Diabetes & Endocrinology. The study did not meet its primary endpoint: at 12 months, insulin production, as measured by C-peptide responses, showed no difference in overall decline between the treatment and placebo groups.
Thymoglobulin®, currently licensed for the treatment of organ ...
Broccoli could be key in the fight against osteoarthritis
2013-08-28
A compound found in broccoli could be key to preventing or slowing the progress of the most common form of arthritis, according to new research led by the University of East Anglia (UEA).
Results from the laboratory study show that sulforaphane slows down the destruction of cartilage in joints associated with painful and often debilitating osteoarthritis. The researchers found that mice fed a diet rich in the compound had significantly less cartilage damage and osteoarthritis than those that were not.
The study, which also examined human cartilage cells and cow cartilage ...
Joslin scientists identify genetic variant associated with coronary heart disease in type 2 diabetes
2013-08-28
BOSTON -- August 27, 2013 -- Joslin scientists, in collaboration with researchers from the Harvard School of Public Health and Italian research institutes, have identified a previously unknown genetic variant associated with an increased risk of coronary heart disease (CHD) in type 2 diabetic patients. This discovery has the potential to lead to the development of new treatments for CHD in diabetic patients. The findings appear in the [month] issue of the Journal of the American Medical Association (JAMA).
CHD is the leading cause of morbidity and mortality among diabetic ...
Genetic variant identified that may increase heart disease risk among people with type 2 diabetes
2013-08-28
Boston, MA — A newly discovered genetic variant may increase the risk of heart disease in people with type 2 diabetes by more than a third, according to a study led by researchers at Harvard School of Public Health (HSPH) and Joslin Diabetes Center. It is the first genome-wide association study (GWAS) to identify a novel genetic variant associated with coronary heart disease (CHD) in people with type 2 diabetes, who have a two- to four-fold higher risk of heart disease compared with those without diabetes. The finding could lead to new interventions aimed at preventing ...
Zealous imaging fuelling unnecessary and harmful treatment of low risk thyroid cancers
2013-08-28
New technologies such as ultrasound, CT and MRI scanning can detect thyroid nodules as small as 2mm – many of these small nodules are papillary thyroid cancers.
In the US, cases have tripled in the past 30 years - from 3.6 per 100,000 in 1973 to 11.6 per 100,000 in 2009 – making it one of the fastest growing diagnoses. Yet the death rate from papillary thyroid cancer has remained stable.
This expanding gap between incidence of thyroid cancer and deaths suggests that low risk cancers are being overdiagnosed and overtreated, argue Dr Juan Brito and colleagues at the ...
The extraordinary evolution of REVs
2013-08-28
A new study by Anna Maria Niewiadomska and Robert Gifford, of The Aaron Diamond AIDS Research Center, New York, reveals that reticuloendotheliosis viruses (REVs), which originated in mammals, spread to birds as a result of medical intervention. Their findings will be published August 27 in the open access journal PLOS Biology.
"We became intrigued by these viruses", says Gifford, "…because their distribution in nature suggests something very unusual has occurred during their evolution."
The reticuloendotheliosis viruses (REVs) are retroviruses that were first identified ...
LAST 30 PRESS RELEASES:
Unlocking the mysteries of the human gut
High-quality nanodiamonds for bioimaging and quantum sensing applications
New clinical practice guideline on the process for diagnosing Alzheimer’s disease or a related form of cognitive impairment or dementia
Evolution of fast-growing fish-eating herring in the Baltic Sea
Cryptographic protocol enables secure data sharing in the floating wind energy sector
Can drinking coffee or tea help prevent head and neck cancer?
Development of a global innovative drug in eye drop form for treating dry age-related macular degeneration
Scientists unlock secrets behind flowering of the king of fruits
Texas A&M researchers illuminate the mysteries of icy ocean worlds
Prosthetic material could help reduce infections from intravenous catheters
Can the heart heal itself? New study says it can
Microscopic discovery in cancer cells could have a big impact
Rice researchers take ‘significant leap forward’ with quantum simulation of molecular electron transfer
Breakthrough new material brings affordable, sustainable future within grasp
How everyday activities inside your home can generate energy
Inequality weakens local governance and public satisfaction, study finds
Uncovering key molecular factors behind malaria’s deadliest strain
UC Davis researchers help decode the cause of aggressive breast cancer in women of color
Researchers discovered replication hubs for human norovirus
SNU researchers develop the world’s most sensitive flexible strain sensor
Tiny, wireless antennas use light to monitor cellular communication
Neutrality has played a pivotal, but under-examined, role in international relations, new research shows
Study reveals right whales live 130 years — or more
Researchers reveal how human eyelashes promote water drainage
Pollinators most vulnerable to rising global temperatures are flies, study shows
DFG to fund eight new research units
Modern AI systems have achieved Turing's vision, but not exactly how he hoped
Quantum walk computing unlocks new potential in quantum science and technology
Construction materials and household items are a part of a long-term carbon sink called the “technosphere”
First demonstration of quantum teleportation over busy Internet cables
[Press-News.org] St. Jude Children's Research Hospital scientists identify ALS disease mechanismStudy strengthens link between amyotrophic lateral sclerosis and problems in protein production machinery of cells and identifies possible treatment strategy