Posts tagged neurodegeneration
Articles and news from the latest research reports.
Accused of complicity in Alzheimer’s, amyloid proteins may be getting a bad rap
Amyloids — clumps of misfolded proteins found in the brains of people with Alzheimer’s disease and other neurodegenerative disorders — are the quintessential bad boys of neurobiology. They’re thought to muck up the seamless workings of the neurons responsible for memory and movement, and researchers around the world have devoted themselves to devising ways of blocking their production or accumulation in humans.
But now a pair of recent research studies from the Stanford University School of Medicine sets a solid course toward rehabilitating the reputation of the proteins that form these amyloid tangles, or plaques. In the process, they appear poised to turn the field of neurobiology on its head.
The first study, published in August, showed that an amyloid-forming protein called beta amyloid, which is strongly implicated in Alzheimer’s disease, could reverse the symptoms of a multiple-sclerosis-like neurodegenerative disease in laboratory mice.
The second study, published April 3 in Science Translational Medicine, extends the finding to show that small portions of several notorious amyloid-forming proteins (including well-known culprits like tau and prion proteins) can also quickly alleviate symptoms in mice with the condition — despite the fact that the fragments can and do form the long tendrils, or fibrils, previously thought harmful to nerve health.
“What we’re finding is that, at least under certain circumstances, these amyloid peptides actually help the brain,” said Lawrence Steinman, MD, professor of neurology and neurological sciences and of pediatrics. “This really turns the ‘amyloid-is-bad’ dogma upside down. It will require a shift in people’s fundamental beliefs about neurodegeneration and diseases like multiple sclerosis, Alzheimer’s and Parkinson’s.”
Steinman is a noted expert in multiple sclerosis whose research led to the development of natalizumab (marketed as Tysabri), a potent treatment for the disease.
Taken together, the studies begin to suggest the radical new idea that full-length, amyloid-forming proteins may in fact be produced by the body as a protective, rather than destructive, force. In particular, Steinman’s study shows that these proteins may function as molecular chaperones, escorting and removing from sites of injury specific molecules involved in inflammation and inappropriate immune responses.
Steinman, who is also the medical school’s George A. Zimmermann Professor, is the corresponding author of the research. Jonathan Rothbard, PhD, a senior research scientist in the Steinman laboratory, is the senior author; postdoctoral scholar Michael Kurnellas, PhD, is the lead author.
Although the specific findings of Steinman’s two studies are surprising, there have been inklings from previous research that amyloid-forming proteins may not be all bad. In particular, inhibiting, or knocking out, the expression of several of the proteins in the mouse models of multiple sclerosis — a technique that should block the course of the disease if these proteins are the cause — instead worsened the animals’ symptoms.
And there’s the fact that these so-called dangerous amyloid-forming molecules are surprisingly prevalent. “We know the body makes a lot of amyloid-forming proteins in response to injury,” said Steinman. “I’m doubtful that that’s done to produce more harm. For example, the prion protein is found in every cell in our bodies. What is it doing? It’s possible that any therapeutic maneuver to remove all of these proteins could interfere with their natural function.”
Understanding how amyloids form requires an understanding of the biology of proteins, which are essentially strings of smaller components called amino acids attached end to end. Once they’re made, these protein strings twist and fold into specific three-dimensional shapes that fit together like keys and locks to do the work of the cell.
A misfolded protein is likely to be unable to carry out its duties and must be disposed of by the body’s cellular waste-management system. Amyloid-forming proteins (of which there are around 20), however, don’t go quietly, if at all. Instead, they initiate a chain reaction with other misfolded proteins — forming long, insoluble strands called fibrils that mat together to form amyloid clumps. These clumps appear consistently in the brains of people with neurodegenerative diseases like Alzheimer’s and multiple sclerosis, but not in the brains of healthy people.
Although these clumps are thought to be detrimental to nerve cells, it’s not entirely clear how they cause harm. One possibility is the ability of the fibrils to form cylindrical pores that could disrupt the cellular membrane and interfere with the orderly flow of ions and molecules used by the cells to communicate and transmit nerve signals. Regardless, their very presence suggests a diagnosis of neurodegeneration to many clinicians, including — until recently — Steinman.
“We began this research because these molecules are present in the brains of people with multiple sclerosis,” said Steinman. “We expected to show that the presence of beta amyloid made the disease worse in laboratory animals. Instead, we saw a great deal of benefit.”
Intrigued by the results of their first study, the researchers next tested the effect of small, six-amino-acid portions of several amyloid-forming proteins, including beta amyloid, which appeared likely to share a three-dimensional structure. They found that nearly all of the tiny protein molecules, or hexamers, were also able to temporarily reverse the symptoms of multiple sclerosis in the mice (when the treatment was stopped, the mice developed signs of the condition within a few days).
The researchers noted, however, that the curative effect of the hexamers was linked to their ability to form fibrils similar, but not identical, to their longer parent molecules. For example, these simplified hexamer fibrils are more easily formed and broken apart than those composed of whole proteins. They are also thought not to be able to form the cylindrical pores that might damage cell membranes. Finally, the hexamer fibrils appear to inhibit the formation of fibrils from full-length proteins — perhaps by blocking, or failing to promote, the chain reaction that initiates fibril formation.
When Steinman and his colleagues mixed the fibril-forming hexamers with blood plasma from three people with multiple sclerosis, they found that the fibrils bound to and removed from solution many potentially damaging molecules involved in inflammation and the immune response.
“These hexamer fibrils appear to be working to remove dangerous chemicals from the vicinity of the injury,” said Steinman.
The researchers are eager to pursue the use of these small hexamers as therapies for neurodegenerative diseases like multiple sclerosis. Much research is still needed, but Steinman is hopeful.
“The lessons we learn from our study of amyloid-forming proteins in multiple sclerosis could be helpful for stroke and brain trauma, as well as for Alzheimer’s,” said Steinman. “We’re gaining insight into how current therapeutic approaches may be affecting the body, and beginning to understand the nuances necessary to design a successful treatment. Although it will take time, we’re determined to move promising results out of the laboratory and into the clinic as quickly as possible.”
(Image: Wikimedia Commons)
Infant brains imply adult ills: Researchers study traits in babies as young as two weeks
Brain images from newborns are giving scientists a glimpse of the future - not just into the lives of their tiny subjects but also paths to treatment for adult patients with schizophrenia and Alzheimer’s disease.
Researchers from the University of North Carolina-Chapel Hill found degeneration in the brains of 2-week-old infants, a result considered a “game changer” for the field of brain research, said Jay Giedd, a brain imaging specialist for the National Institute of Mental Health.
"Our original model was that the brain was fine until someone got the illness," Giedd said. "This work shows that these changes are there probably from conception. It also suggests that while these traits don’t cause brain damage, they set up the brain to be slightly different."
The researchers examined scans of 272 newborns. About 15 percent were found to have smaller medial temporal lobe sections. “The medial temporal lobe plays an important role in memory,” said Rebecca Knickmeyer, a UNC assistant professor of psychiatry and co-author of the research, published last month in Cerebral Cortex, an online journal.
"The idea is that this is an anatomical vulnerability. If you start out with less, you might hit active symptoms earlier in life."
The researchers also found specific gene traits associated with Alzheimer’s in babies with the smaller media temporal lobes.
"We were interested because it was generally known that people’s genes contribute to psychiatric conditions later in life, but pretty much all the existing studies were in adults," Knickmeyer said. "Our question was ‘When were these genes exerting their effect?’ Now we know it’s much earlier than previously thought, perhaps before birth."
Research such as this would benefit from the Brain Activity Map under development through the National Institutes of Health. The project’s 10-year goal is to create a map of the brain’s nearly 30,000 genes as well as the circuitry system that transmits information via brain waves.
President Obama mentioned the project in his State of the Union address and is expected to include funding for the project in the upcoming federal budget. Foundations and some private companies have also expressed interest in assisting in the project, which is expected to push brain research to a higher level.
"As brain scientists, we were giddy to hear this," Giedd said. "Motivation is sky high. If they fund this, we believe our work will really take off." Giedd, who is familiar with but did not participate in the infant brain study, said the search for treatments or cures for diseases such as Alzheimer’s, autism, schizophrenia and Parkinson’s disease have been stymied by the many mysteries that remain regarding how the brain functions.
"If we understood more about the mechanisms that cause these diseases, we could step in and do something about it," Giedd said. "The brain is so complicated. Most diseases don’t just involve one or two or even three genes. It might be 60 or 100 genes, along with upbringing, diet and environment. There are so many parameters to the equation."
Knickmeyer said her research team plans to follow up with the newborns as they grow into adulthood to see whether the traits displayed by infants change over time or remain stable throughout their lives.
Daniel Kaufer, cognitive neurology and memory disorders chief for UNC’s Department of Neurology, said he thinks the time is right for great advances in brain research.
"We are at the crossroads of two important events: the realization that brain disorders may occur long before symptoms begin, and the development of brain imaging technology to record brain processes," Kaufer said.
Learning more about the brain’s functions through gene mapping may be the third piece of the puzzle. “Right now, there is no map of the human brain,” said Murali Doraiswamy, professor of psychiatry and behavioral sciences at Duke University School of Medicine.
Doraiswamy said the brain carries thousands of genes that influence thought, perception, emotion, memory and other mental activities. “We want to find out how much is nature and how much is nurture,” he added. “I think we are at the forefront of something very insightful, but also a little frightening.”
MAPPING A NEW WORLD
The Brain Activity Map is being planned as a decade-long research effort to create a comprehensive outline of the structure of the human brain and its neurons.
Funding is expected to come from a variety of sources, including the federal government, private industry and research foundations.
Details of the project have not yet been made public. But it is being compared to the DNA sequencing effort known as the Human Genome Project, which ran from 1990 to 2003 and cost $3.8 billion.
A how-to manual for fruit fly research has been created
The first ever basic training package to teach students and scientists how to best use the fruit fly, Drosophila, for research has been published. It’s hoped it will encourage more researchers working on a range of conditions from cancer to Alzheimer’s disease to use the humble fly.
The unique scheme has been put together by Dr Andreas Prokop from the Faculty of Life Sciences at the University of Manchester and John Roote from the Department of Genetics at the University of Cambridge.
John Roote said, “In 1910 Thomas Hunt Morgan isolated the first Drosophila sex-linked mutation, white. Since then many thousands of research workers have realised the potential of the humble fruit fly.
“The powerful research tools that we have today combined with a century of background knowledge, the vast collections of stocks that are available to everyone and the fortuitous ‘pre-adaptation’ of the fly for life in a laboratory ensure that Drosophila melanogaster maintains its position as the pre-eminent model organism for research in genetics. However, until now a comprehensive teaching programme to guide students through the often daunting first few steps has been surprisingly absent.”
Dr Prokop said: “People don’t realise just how useful the tiny fruit fly can be when it comes to research. Fellow scientists are often not aware of their genetic value for research. For example, about 75% of known human disease genes have a recognisable match in the genome of fruit flies which means they can be used to study the fundamental biology behind complex conditions such as epilepsy or neurodegeneration.”
Fruit flies have been used for scientific research for more than a hundred years. They have allowed scientific breakthroughs in genetics, body structure and function. The first jet lag gene and the first learning gene were identified in flies as well as breakthroughs in neuroscience, such as the discovery of the first channel proteins.
Training package: How to design a genetic mating scheme: a basic training package for Drosophila genetics
Neuronal activity induces tau release from healthy neurons
Researchers from King’s College London have discovered that neuronal activity can stimulate tau release from healthy neurons in the absence of cell death. The results published by Diane Hanger and her colleagues in EMBO reports show that treatment of neurons with known biological signaling molecules increases the release of tau into the culture medium. The release of tau from cortical neurons is therefore a physiological process that can be regulated by neuronal activity.
Tau proteins stabilize microtubules, the long threads of polymers that help to maintain the structure of the cell. However, in Alzheimer’s disease or certain types of dementia, tau accumulates in neurons or glial cells, where it contributes to neurodegeneration.
In addition to intracellular aggregation, recent experiments have shown that tau is released from neuronal cells and taken up by neighboring cells, which allows the spread of aggregated tau across the brain. This release could occur passively from dying neuronal cells, though some evidence suggests it might take place before neuronal cell death and neurodegeneration. The new findings indicate that tau release is an active process in healthy neurons and this could be altered in diseased brains.
“Our findings suggest that altered tau release is likely to occur in response to changes in neuronal excitability in the Alzheimer’s brain. Secreted tau could therefore be involved in the propagation of tau pathology in tauopathies, a group of neurodegenerative diseases associated with the accumulation of tau proteins in the brain,” commented Diane Hanger, Reader in the Department of Neuroscience at King’s College London. In these experiments, Amy Pooler, the lead author, revealed that molecules such as potassium chloride, glutamate or an AMPA receptor agonist could release tau from cortical neurons in an active physiological process that is, at least partially, dependent on pre-synaptic vesicle secretion.
The new findings by the scientists indicate that tau has previously unknown roles in biological signaling between cells, in addition to its well-established role in stabilizing microtubules.
“We believe that targeting the release of tau could be explored as a new therapeutic approach for the treatment of Alzheimer’s disease and related tauopathies,” said Hanger. Additional studies are needed in model organisms to test this hypothesis further.
(Image: Patrick Hoesly)
Low-protein diet slows Alzheimer’s in mice
Mice with many of the pathologies of Alzheimer’s Disease showed fewer signs of the disease when given a protein-restricted diet supplemented with specific amino acids every other week for four months.
Mice at advanced stages of the disease were put on the new diet. They showed improved cognitive abilities over their non-dieting peers when their memory was tested using mazes. In addition, fewer of their neurons contained abnormal levels of a damaged protein, called “tau,” which accumulates in the brains of Alzheimer’s patients.
Dietary protein is the major dietary regulator of a growth hormone known as IGF-1, which has been associated with aging and diseases in mice and several diseases in older adults.
Upcoming studies by USC Professor Valter Longo, the study’s corresponding author, will attempt to determine whether humans respond similarly – while simultaneously examining the effects of dietary restrictions on cancer, diabetes and cardiac disease.
"We had previously shown that humans deficient in Growth Hormone receptor and IGF-I displayed reduced incidence of cancer and diabetes. Although the new study is in mice, it raises the possibility that low protein intake and low IGF-I may also protect from age-dependent neurodegeneration," said Longo, who directs the Longevity Institute of the USC Davis School of Gerontology and has a joint appointment the USC Dornsife College of Letters, Arts and Sciences.
Longo worked with Pinchas Cohen, dean of the USC Davis School, as well as USC graduate students Edoardo Parrella, Tom Maxim, Lu Zhang, Junxiang Wan and Min Wei; Francesca Maialetti of the Istituto Superiore di Sanità in Rome; and Luigi Fontana of Washington University in St. Louis.
"Alzheimer’s Disease and other forms of neurodegeneration are a major burden on society, and it is a rising priority for this nation to develop new approaches for preventing and treating these conditions, since the frequencies of these disorders will be rising as the population ages over the next several decades," said Cohen, who became dean of the School of Gerontology in summer 2012. "New strategies to address this, particularly non-invasive, non-pharmacological approaches such as tested in Dr. Longo’s study are particularly exciting."
The results of their study were published online by Aging Cell last month.
The team found that a protein-restricted diet reduced levels of IGF-1 circulating through the body by 30 to 70 percent, and caused an eight-fold increase in a protein that blocks IGF-1’s effects by binding to it.
IGF-1 helps the body grow during youth but is also associated with several diseases later in life in both mice and humans. Exploring dietary solutions to those diseases as opposed to generating pharmaceuticals to manipulate IGF-1 directly allows Longo’s team to make strides that could help sufferers today or in the next few years.
"We always try to do things for people who have the problem now," Longo said. "Developing a drug can take 15 years of trials and a billion dollars.
"Although only clinical trials can determine whether the protein-restricted diet is effective and safe in humans with cognitive impairment, a doctor could read this study today and, if his or her patient did not have any other viable options, could consider introducing the protein restriction cycles in the treatment – understanding that effective interventions in mice may not translate into effective human therapies," he said.
Many elderly individuals may have already be frail, have lost weight or may not be healthy enough to eat a protein-restricted diet every other week. Longo strongly insisted that any dieting be monitored by a doctor or registered dietician to make sure that patients do not become amino acid deficient, lose additional weight or develop other side effects.
(Source: eurekalert.org)
Cell Loss in the Brain Relates to Variations in Individual Symptoms in Huntington’s Disease
Scientists have wrestled to understand why Huntington’s disease, which is caused by a single gene mutation, can produce such variable symptoms. An authoritative review by a group of leading experts summarizes the progress relating cell loss in the striatum and cerebral cortex to symptom profile in Huntington’s disease, suggesting a possible direction for developing targeted therapies. The article is published in the latest issue of the Journal of Huntington’s Disease.
Huntington’s disease (HD) is an inherited progressive neurological disorder for which there is presently no cure. It is caused by a dominant mutation in the HD gene leading to expression of mutant huntingtin (HTT) protein. Expression of mutant HTT causes subtle changes in cellular functions, which ultimately results in jerking, uncontrollable movements, progressive psychiatric difficulties, and loss of mental abilities.
Although it is caused by a single gene, there are major variations in the symptoms of HD. The pattern of symptoms shown by each individual during the course of the disease can differ considerably and present as varying degrees of movement disturbances, cognitive decline, and mood and behavioral changes. Disease duration is typically between ten and twenty years.
Recent investigations have focused on what the presence of the defective gene does to various structures in the brain and understanding the relationship between changes in the brain and the variability in symptom profiles in Huntington’s disease.
Analyses of post-mortem human HD tissue suggest that the variation in clinical symptoms in HD is strongly associated with the variable pattern of neurodegeneration in two major regions of the brain, the striatum and the cerebral cortex. The neurodegeneration of the striatum generally follows an ordered and topographical distribution, but comparison of post-mortem human HD tissue and in vivo neuroimaging techniques reveal that the disease produces a striking bilateral atrophy of the striatum, which in these recent studies has been found to be highly variable.
“What is especially interesting is that recent findings suggest that the pattern of striatal cell death shows regional differences between cases in the functionally and neurochemically distinct striosomal and matrix compartments of the striatum which correspond with symptom variation,” says author Richard L.M. Faull, MB, ChB, PhD, DSc, Director of the Centre for Brain Research, University of Auckland, New Zealand.
“Our own recent detailed quantitative study using stereological cell counting in the post-mortem human HD cortex has complemented and expanded the neuroimaging studies by providing a cortical cellular basis of symptom heterogeneity in HD,” continues Dr Faull. “In particular, HD cases which were dominated by motor dysfunction showed a major total cell loss (28% loss) in the primary motor cortex but no cell loss in the limbic cingulate cortex, whereas cases where mood symptoms predominated showed a total of 54% neuronal loss in the limbic cingulate cortex but no cell loss in the motor cortex. This suggests that the variable neuronal loss and alterations in the circuitry of the primary motor cortex and anterior cingulate cortex associated with the variable compartmental pattern of cell degeneration in the striatum contribute to the differential impairments of motor and mood functions in HD.”
The authors note that there are still questions to be answered in the field of HD pathology, such as, how and when pathological neuronal loss occurs; whether the progressive loss of neurons in the striatum is the primary process or is consequential to cortical cell dysfunction; and how these changes relate to symptom profiles.
“What is clear however is that the diverse symptoms of HD patients appear to relate to the heterogeneity of cell loss in both the striatum and cerebral cortex,” the authors conclude. “While there is currently no cure, this contemporary evidence suggests that possible genetic therapies aimed at HD gene silencing should be directed towards intervention at both the cerebral cortex and the striatum in the human brain. This poses challenging problems requiring the application of gene silencing therapies to quite widespread regions of the forebrain which may be assisted via CSF delivery systems using gene suppression agents that cross the CSF/brain barrier.”
(Source: iospress.nl)
Promising compound restores memory loss and reverses symptoms of Alzheimer’s
A new ray of hope has broken through the clouded outcomes associated with Alzheimer’s disease. A new research report published in January 2013 print issue of The FASEB Journal by scientists from the National Institutes of Health shows that when a molecule called TFP5 is injected into mice with disease that is the equivalent of human Alzheimer’s, symptoms are reversed and memory is restored—without obvious toxic side effects.
"We hope that clinical trial studies in AD patients should yield an extended and a better quality of life as observed in mice upon TFP5 treatment," said Harish C. Pant, Ph.D., a senior researcher involved in the work from the Laboratory of Neurochemistry at the National Institute of Neurological Disorders at Stroke at the National Institutes of Health in Bethesda, MD. "Therefore, we suggest that TFP5 should be an effective therapeutic compound."
To make this discovery, Pant and colleagues used mice with a disease considered the equivalent of Alzheimer’s. One set of these mice were injected with the small molecule TFP5, while the other was injected with saline as placebo. The mice, after a series of intraperitoneal injections of TFP5, displayed a substantial reduction in the various disease symptoms along with restoration of memory loss. In addition, the mice receiving TFP5 injections experienced no weight loss, neurological stress (anxiety) or signs of toxicity. The disease in the placebo mice, however, progressed normally as expected. TFP5 was derived from the regulator of a key brain enzyme, called Cdk5. The over activation of Cdk5 is implicated in the formation of plaques and tangles, the major hallmark of Alzheimer’s disease.
"The next step is to find out if this molecule can have the same effects in people, and if not, to find out which molecule will," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. “Now that we know that we can target the basic molecular defects in Alzheimer’s disease, we can hope for treatments far better – and more specific – than anything we have today.”
(Source: eurekalert.org)
Houston, We Have Another Problem: Study Shows that Space Travel is Harmful to the Brain
As if space travel was not already filled with enough dangers, a new study out today in the journal PLOS ONE shows that cosmic radiation – which would bombard astronauts on deep space missions to places like Mars – could accelerate the onset of Alzheimer’s disease.
“Galactic cosmic radiation poses a significant threat to future astronauts,” said M. Kerry O’Banion, M.D., Ph.D., a professor in the University of Rochester Medical Center (URMC) Department of Neurobiology and Anatomy and the senior author of the study. “The possibility that radiation exposure in space may give rise to health problems such as cancer has long been recognized. However, this study shows for the first time that exposure to radiation levels equivalent to a mission to Mars could produce cognitive problems and speed up changes in the brain that are associated with Alzheimer’s disease.”
While space is full of radiation, the earth’s magnetic field generally protects the planet and people in low earth orbit from these particles. However, once astronauts leave orbit, they are exposed to constant shower of various radioactive particles. With appropriate warning, astronauts can be shielded from dangerous radiation associated with solar flares. But there are also other forms of cosmic radiation that, for all intents and purposes, cannot be effectively blocked.
Because this radiation exists in low levels, the longer an astronaut is in deep space, the greater the exposure. This is a concern for NASA as the agency is planning manned missions to a distant asteroid in 2021 and to Mars in 2035. The round trip to the red planet, in particular, could take as long as three years.
For over 25 years, NASA has been funding research to determine the potential health risks of space travel in an effort to both develop countermeasures and determine whether or not the risks warranted sending men and women on extended missions in deep space.
Since that time, several studies have demonstrated the potential cancer, cardiovascular, and musculoskeletal impact of galactic cosmic radiation. The study out today for the first time examines the potential impact of space radiation on neurodegeneration, in particular, the biological processes in the brain that contribute to the development of Alzheimer’s disease. O’Banion – whose research focuses on how radiation affects the central nervous system – and his team have been working with NASA for over eight years.
The researchers studied the impact of a particular form of radiation called high-mass, high-charged (HZE) particles. These particles – which are propelled through space at very high speeds by the force of exploding stars – come in many different forms. For this study the researcher chose iron particles. Unlikely hydrogen protons, which are produced by solar flares, the mass of HZE particles like iron, combined with their speed, enable them to penetrate solid objects such as the wall and protective shielding of a spacecraft.
“Because iron particles pack a bigger wallop it is extremely difficult from an engineering perspective to effectively shield against them,” said O’Banion. “One would have to essentially wrap a spacecraft in a six-foot block of lead or concrete.”
Mayo Clinic Researchers Uncover Toxic Interaction in Neurons that Leads to Dementia and ALS
Researchers at Mayo Clinic in Florida have uncovered a toxic cellular process by which a protein that maintains the health of neurons becomes deficient and can lead to dementia. The findings shed new light on the link between culprits implicated in two devastating neurological diseases: frontotemporal dementia and amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease. The study is published Dec. 10 in the online issue of Proceedings of the National Academy of Sciences.
There is no cure for frontotemporal dementia, a disorder that affects personality, behavior and language and is second only to Alzheimer’s disease as the most common form of early-onset dementia. While much research is devoted to understanding the role of each defective protein in these diseases, the team at Mayo Clinic took a new approach to examine the interplay between TDP-43, a protein that regulates messenger ribonucleic acid (mRNA) — biological molecules that carry the information of genes and are used by cells to guide protein synthesis — and sortilin, which regulates the protein progranulin.
"We sought to investigate how TDP-43 regulates the levels of the protein progranulin, given that extreme progranulin levels at either end of the spectrum, too low or too high, can respectively lead to neurodegeneration or cancer," says the study’s lead investigator, Mercedes Prudencio, Ph.D., a neuroscientist at the Mayo Clinic campus in Florida.
The neuroscientists found that a lack of the protein TDP-43, long implicated in frontotemporal dementia and amyotrophic lateral sclerosis, leads to elevated levels of defective sortilin mRNA. The research team is the first to identify significantly elevated levels of the defective sortilin mRNA in autopsied human brain tissue of frontotemporal dementia/TDP cases, the most common subtype of the disease.
(Image: Wikimedia Commons)
Scientists image brain structures that deteriorate in Parkinson’s
A new imaging technique developed at MIT offers the first glimpse of the degeneration of two brain structures affected by Parkinson’s disease.
The technique, which combines several types of magnetic resonance imaging (MRI), could allow doctors to better monitor patients’ progression and track the effectiveness of potential new treatments, says Suzanne Corkin, MIT professor emerita of neuroscience and leader of the research team. The first author of the paper is David Ziegler, who received his PhD in brain and cognitive sciences from MIT in 2011.
The study, appearing in the Nov. 26 online edition of the Archives of Neurology, is also the first to provide clinical evidence for the theory that Parkinson’s neurodegeneration begins deep in the brain and advances upward.
“This progression has never been shown in living people, and that’s what was special about this study. With our new imaging methods, we can see these structures more clearly than anyone had seen them before,” Corkin says.