Posts tagged nerve cells
Articles and news from the latest research reports.
Travelling by resonance
How nerve cells within the brain communicate with each other over long distances has puzzled scientists for decades. The way networks of neurons connect and how individual cells react to incoming pulses in principle makes communication over large distances impossible. Scientists from Germany and France provide now a possible answer how the brain can function nonetheless: by exploiting the powers of resonance.
(Image caption: Resonance in the activity of nerve cells (left) allows activity within the brain to travel over large distances, e.g. from the back of the head to the front during the processing of visual stimuli. Credit: Gunnar Grah/BrainLinks-BrainTools)
As Gerald Hahn, Alejandro F. Bujan and colleagues describe in the journal “PLoS Computational Biology”, the ability of networks of neurons to resonate can amplify oscillations in the activity of nerve cells, allowing signals to travel much farther than in the absence of resonance. The team from the cluster of excellence BrainLinks-BrainTools and the Bernstein Center at the University of Freiburg and the UNIC department of the French Centre national de la recherche scientifique in Gif-sur-Yvette created a computer model of networks of nerve cells and analyzed its properties for signal propagation.
Earlier propositions how information travels through the brain had the flaw of being biologically implausible. They either postulated strong connections between distant brain areas for which there was no evidence, or they required a global mechanism setting these distant parts of the brain into linked oscillations. However, nobody could explain how this could actually be implemented.
The simulation study of Hahn and Bujan required neither unrealistic network properties nor the existence of a pacemaker for the brain. Instead, they found that resonance could be the key to long-distance communication in networks with relatively few and weak connections, as it is the case in the brain. Not all nerve cells excite other cells; some inhibit the activity of others. This means that the activity in a network can oscillate around a certain level of activity as a result of the interplay of excitation and inhibition. These networks typically have preferred frequencies at which oscillations are particularly strong, just as a taut string on a violin has a preferred frequency. If the activity tunes into this frequency, pulses propagate much farther. As the scientists point out, the combination of oscillatory signals together with resonance induced amplification may be the only possible form of long distance communication in certain cases. They further suggest that a network’s ability to change its preferred frequency may play a role in the way how information is at times processed differently in the brain.
(Source: pr.uni-freiburg.de)
How Alzheimer’s Peptides Shut Down Cellular Powerhouses
The failing in the work of nerve cells: An international team of researchers led by Prof. Dr. Chris Meisinger from the Institute of Biochemistry and Molecular Biology of the University of Freiburg has discovered how Alzheimer’s disease damages mitochondria, the powerhouses of the cell. For several years researchers have known that the cellular energy supply of brain cells is impaired in Alzheimer’s patients. They suspect this to be the cause of premature death of nerve cells that occurs in the course of the disease. Little is known about the precise cause of this neuronal cell death, and many approaches and attempts to find an effective therapy have failed to make an impact. What is certain is that a tiny protein fragment by the name of “amyloid-beta” plays a key role in the process. Meisinger, a member of the Cluster of Excellence BIOSS Centre for Biological Signalling Studies of the University of Freiburg, and his team have now demonstrated how this protein fragment blocks the maturation of protein machines that are responsible for the production of energy inside the cellular powerhouses. The researchers demonstrated this with the help of model organisms and with brain samples from Alzheimer’s patients. “The elucidation of this key component of the disease mechanism will enable us to develop new therapies and improve diagnostics in the future,” explains Meisinger. The findings were published in the journal Cell Metabolism.
Mitochondria are made up of around 1500 different proteins. Most of them need to migrate to the cellular powerhouses before taking up their work. This import is facilitated by a so-called signaling sequence – tiny protein extensions that transport the protein into the mitochondria. Once the protein is inside, the signaling sequence is normally removed. Dirk Mossmann and Dr. Nora Vögtle from Meisinger’s research team have now discovered that the amyloid-beta peptide prevents mitochondria from removing these signaling sequences. As a consequence, incomplete proteins accumulate in the mitochondria. Since the signaling sequences remain attached, the proteins are unstable and can no longer adequately carry out their function in energy metabolism. The researchers demonstrated that modified yeast cells producing the amyloid-beta protein generate less energy and accumulate more harmful substances.
In the brain, the mechanism probably leads to the death of nerve cells: The brain shrinks and the patient suffers from dementia. The researchers are currently developing an Alzheimer’s blood test to detect the accumulation of mitochondrial precursor proteins. They suspect that the mitochondrial alterations observed in nerve cells will also be detected in the blood cells of Alzheimer’s patients.
(Source: pr.uni-freiburg.de)
Scientists Uncover Navigation System Used by Cancer, Nerve Cells
Duke University researchers have found a ”roving detection system” on the surface of cells that may point to new ways of treating diseases like cancer, Parkinson’s disease and amyotrophic lateral sclerosis (ALS).
The cells, which were studied in nematode worms, are able to break through normal tissue boundaries and burrow into other tissues and organs — a crucial step in many normal developmental processes, ranging from embryonic development and wound-healing to the formation of new blood vessels.
But sometimes the process goes awry. Such is the case with metastatic cancer, in which cancer cells spread unchecked from where they originated and form tumors in other parts of the body.
“Cell invasion is one of the most clinically relevant yet least understood aspects of cancer progression,” said David Sherwood, an associate professor of biology at Duke.
Sherwood is leading a team that is investigating the molecular mechanisms that control cell invasion in both normal development and cancer, using a one-millimeter worm known as C. elegans.
At one point in C. elegans development, a specialized cell called the anchor cell breaches the dense, sheet-like membrane that separate the worm’s uterus from its vulva, opening up the worm’s reproductive tract.
Anchor cells can’t see, so they need some kind of signal to tell them where to break through. In a 2009 study, Sherwood and colleagues discovered that an extracellular cue called netrin orients the anchor cell so that it invades in the right direction.
In a new study appearing Aug. 25 in the Journal of Cell Biology, the team shows how receptors on the invasive cells essentially rove around the cell membrane ”hunting” for the missing netrin signal that will guide the cell to the correct location.
The researchers used a video camera attached to a powerful microscope to take time-lapse movies of the slow movement of the C. elegans anchor cell during its invasion (Figure 1, Figure 2).
Their time-lapse analyses reveal that when netrin production is blocked, netrin receptors on the surface of the anchor cell periodically cluster, disperse and reassemble in a different region of the cell membrane. The receptors cluster alongside patches of actin filaments — thin flexible fibers that help cells change shape and form invasive protrusions –- that pop up in each new spot.
“It’s kind of like a missile detection system,” Sherwood said.
Rather than the whole cell having to move around, its receptors move around on the outside of the cell until they get a signal. Once the receptors locate the netrin signal, they stabilize in the region of the cell membrane that is closest to the source of the signal.
The findings redefine decades-old ideas about how the cell’s navigation system works. “Cells don’t just passively respond to the netrin signal — they’re actively searching for it,” Sherwood said.
Given that netrin has been found to promote cell invasion in some of the most lethal cancers, the findings could lead to new treatment strategies. Disrupting the cell’s netrin detection system, for example, could prevent cancer cells from finding their way to the bloodstream or the lymphatic system and stop them from metastasizing, or becoming invasive and spreading throughout the body.
“One of the things we’re gearing up to do next are drug screens with our collaborators to see if we can block this detection system during invasion,” Sherwood said.
Scientists have also known for years that netrin plays a key role in wiring the brain and nervous system by guiding developing nerve cells as they grow and form connections.
This means the results could also point to new ways of treating neurological disorders like Parkinson’s and ALS and recovering from spinal cord injuries.
Tinkering with the cell’s netrin detection machinery, for example, may make it possible to encourage damaged cells in the central nervous system — which normally have limited ability to regenerate — to regrow.
(Source: today.duke.edu)
Stem Cell Therapies Hold Promise, But Obstacles Remain
In an article appearing online today in the journal Science, a group of researchers, including University of Rochester neurologist Steve Goldman, M.D., Ph.D., review the potential and challenges facing the scientific community as therapies involving stem cells move closer to reality.
The review article focuses on pluripotent stem cells (PSCs), which are stem cells that can give rise to all cell types. These include both embryonic stem cells, and those derived from mature cells that have been “reprogrammed” or “induced” – a process typically involving a patient’s own skin cells – so that they possess the characteristics of stem cells found at the earliest stage of development. These cells can then be differentiated, through careful manipulation of chemical and genetic signaling, to become virtually any cell type found in the body.
While the process of making induced PSCs is relatively new in scientific terms – it was first demonstrated that skin cells could be successfully reprogrammed in 2007 – one of the reasons that these cells are viewed with promise by the scientific community is because they are derived from the patient’s own tissue. Consequently, cells used for transplant can be a genetic match and far less likely to be rejected, thereby potentially mitigating the need to use immune system suppressing drugs.
The article addresses the current state of efforts to apply PSCs to treat a number of diseases, including diabetes, liver disease, and heart disease. Goldman, a distinguished professor and co-director of the University of Rochester School of Medicine and Dentistry Center for Translational Neuromedicine, reviewed the current state of therapies for neurological diseases.
While progress has been made over the last several years, the authors point out that significant challenges remain. Scientists must be able to obtain the precise cell populations required to treat the target disease, and once transplanted, make sure that these cells get to where they are needed and integrate into existing tissue. The cells that are transplanted must also first be checked for purity and screened for unwanted cells that could give rise to tumors.
Goldman and his co-authors contend that “the brain is arguable the most difficult of the organs in which to employ stem cell-based therapeutics.” The complex connections and interdependency between neurons and the myriad of other support cells found in central nervous mean that a precise reconstruction of damaged areas of the brain is often impractical. Also, many degenerative neurological disorders, including Alzheimer’s, involve more than one cell type, making them difficult targets for stem cell therapies, at least in the near future.
Instead, Goldman argues that neurological diseases that involve a single cell type – at least at the early stages – are more promising targets for PSC-based therapies. These include Parkinson’s disease and Huntington’s disease, which are characterized by the loss of dopamine-producing neurons and medium spiny neurons, respectively. In particular, diseases that involved support cells found in the brain known as glia – such as multiple sclerosis, white matter stroke, cerebral palsy, and pediatric leukodystrophies – are especially strong candidates for stem cell therapies. These diseases are characterized by the loss of a specific glial cell type called the oligodendrocyte, which makes myelin, the insulation that allows electrical signals to travel between nerve cells. In multiple sclerosis, the body’s own immune system attacks and destroys these cells and, over time, communication between cells is disrupted or even lost.
Oligodendrocytes are the offspring of another cell called the oligodendrocyte progenitor cell, or OPC. Scientists have long speculated that, if successfully transplanted into the diseased or injured brain, OPCs might be able to produce new oligodendrocytes capable of restoring lost myelin, thereby reversing the damage caused by these diseases.
Goldman’s group has already shown that OPCs produced from PSCs obtained from human skin cells successfully restore myelin in the brains and spinal cords of myelin-deficient mice, and can rescue and restore function to mice that would have otherwise died. While this work demonstrated the promise of stem cell therapies, it also illustrated the challenges facing scientists. It took Goldman’s lab four years to establish the exact chemical signaling required to reprogram, produce, and ultimately purify OPCs in sufficient quantities for transplantation, and only recently has the group developed methods for producing the cells in purity and quantity sufficient to transplant into humans.
The authors contend that future progress will depend upon continued close collaboration between scientists and clinicians, and between academia, industry and regulatory bodies to overcome the remaining barriers to bringing new stem cell-based therapies to patients with these devastating diseases.
Scientists find new clues to brain’s wiring
New research provides an intriguing glimpse into the processes that establish connections between nerve cells in the brain. These connections, or synapses, allow nerve cells to transmit and process information involved in thinking and moving the body.
Reporting online in Neuron, researchers at Washington University School of Medicine in St. Louis have identified a group of proteins that program a common type of brain nerve cell to connect with another type of nerve cell in the brain.
The finding is an important step forward in efforts to learn how the developing brain is built, an area of research essential to understanding the causes of intellectual disability and autism.
“We now are looking at how loss of this wiring affects brain function in mice,” said senior author Azad Bonni, MD, PhD, the Edison Professor of Neurobiology and head of the Department of Anatomy and Neurobiology at the School of Medicine.
Bonni and his colleagues are studying synapses in the cerebellum, a region of the brain that sits in the back of the head. The cerebellum plays a central role in controlling the coordination of movement and is essential for what researchers call procedural motor learning, which makes it possible to move our muscles at an unconscious level, such as when we ride a bicycle or play the piano.
“The cerebellum also regulates mental functions,” Bonni said. “So, impairment of the wiring of nerve cells in the cerebellum may contribute to movement disorders as well as cognitive problems including autism spectrum disorders.”
His new results show that a complex of proteins known as NuRD (nucleosome remodeling and deacetylase) plays a fairly high supervisory role in some aspects of the cerebellum’s construction. When the researchers blocked the NuRD complex, cells in the cerebellum called granule cells failed to form connections with other nerve cells, the Purkinje neurons. These circuits are important for the cerebellum’s control of movement coordination and learning.
Bonni and his colleagues showed that NuRD exerts influence at the epigenetic level, which means it controls factors other than DNA that affect gene activity. For example, NuRD affects the configurations of molecules that store DNA and that can open and close the coils of DNA like an accordion, making genes less or more accessible. Changing the accessibility of genes changes their activity levels. For instance, cells can’t frequently make proteins from genes in a tightly packed coil of DNA.
NuRD also alters tags on the proteins that store DNA, decreasing the chances that the gene will be used. Among the genes deactivated by NuRD are two that control the activity of other genes involved in the wiring of the cerebellum.
“This tells us that the NuRD complex is very influential—not only does it affect the activity of genes directly, it also controls other regulators of multiple genes,” Bonni said.
(Image: Courtesy of VJ Wedeen and LL Wald, Martinos Center, Harvard Medical School, Human Connectome Project)
Molecular imbalance linked to brain tumour seizures
Researchers in France may have discovered why some patients with a type of brain tumour have epileptic seizures.
“This small study is interesting and shows that glioma-linked epilepsy may be connected to certain channels found in the membranes of nerve cells” - Dr Robin Grant, Edinburgh Cancer Research UK Centre
Their study, published in Science Translational Medicine, suggests that seizures in patients with glioma may be linked to an imbalance of chloride – which is involved in nerve activity – in certain brain cells.
Whether a patient has seizures is linked to how aggressive their tumour is – with less aggressive cases being more prone to epilepsy as tumour cells slowly progress and alter brain tissue.
It is hoped that further research could explore treatments for glioma-linked epilepsy by controlling chloride levels in the brain.
Glioma develops from specialised brain cells known as ‘glial cells’ that usually help to keep brain nerve cells in place, providing support and protection to ensure correct brain function.
In the latest study, scientists from Sorbonne University studied brain tissue samples from 47 glioma patients and found that nerve tissue infiltrated by glioma cells behaves in similar ways to other forms of epilepsy.
Looking at the patient samples, the team found that a particular type of nerve cell – called a pyramidal cell – released excessive amounts of chloride from inside the cells when exposed to a molecule called GABA, which is also involved in transmitting nerve signals.
GABA was released by other neighbouring nerve cells called ‘interneurons’. And the researchers believe that the release of chloride through specialised molecular channels in the membrane of nerve cells, may be responsible for the seizures experienced in some glioma patients.
Dr Robin Grant, an expert in epilepsy and glioma from the Edinburgh Cancer Research UK Centre, who was not involved in the research, said that the channels may make good drug targets for further investigation, but a finer understanding of the involvement of other processes is still needed.
“This small study is interesting and shows that glioma-linked epilepsy, as with other types of epilepsy, may be connected to certain channels found in the membranes of nerve cells.
“More research will be needed to understand the finer details of this process in glioma and whether these channels, along with other similar channels found in nerve cells, could be good targets for drugs to help control the condition.”
Team Sheds New Light on Nerve Cell Growth
Amidst the astounding complexity of the billions of nerve cells and trillions of synaptic connections in the brain, how do nerve cells decide how far to grow or how many connections to build? How do they coordinate these events within the developing brain?
In a new study, scientists from the Florida campus of The Scripps Research Institute (TSRI) have shed new light on these complex processes, showing that a particular protein plays a far more sophisticated role in neuron development than previously thought.
The study, published in the journal PLOS Genetics, focuses on the large, intracellular signaling protein RPM-1 that is expressed in the nervous system. TSRI Assistant Professor Brock Grill and his team show the surprising degree to which RPM-1 harnesses sophisticated mechanisms to regulate neuron development.
Specifically, the research sheds light on the role of RPM-1 in the development of axons or nerve fibers—the elongated projections of nerve cells that transmit electrical impulses away from the neuron via synapses. Some axons are quite long; in the sciatic nerve, axons run from the base of the spine to the big toe.
“Collectively, our recent work offers significant evidence that RPM-1 coordinates how long an axon grows with construction of synaptic connections,” said Grill. “Understanding how these two developmental processes are coordinated at the molecular level is extremely challenging. We’ve now made significant progress.”
Putting Together the Pieces
The study describes how RPM-1 regulates the activity of a single protein known as DLK-1, a protein that regulates neuron development and plays an essential role in axon regeneration. RPM-1 uses PPM-2, an enzyme that removes a phosphate group from a protein thereby altering its function, in combination with intrinsic ubiquitin ligase activity to directly inhibit DLK-1.
“Studies on RPM-1 have been critical to understanding how this conserved family of proteins works,” said Scott T. Baker, the first author of the study and a member of Grill’s research team. “Because RPM-1 plays multiple roles during neuronal development, you wouldn’t want to interfere with it. But exploring the role of PPM-2 in controlling DLK-1 and axon regeneration could be worthwhile—and could have implications in neurodegenerative diseases.”
The Grill lab has also explored other aspects of how RPM-1 regulates neuron development. A related study, also published in PLOS Genetics, shows that RPM-1 functions as a part of a novel pathway to control β-catenin activity—this is the first evidence that RPM-1 works in connection with extracellular signals, such as a family of protein growth factors known as Wnts, and is part of larger signaling networks that regulate development. A paper in the journal Neural Development shows that RPM-1 is localized at both the synapse and the mature axon tip, evidence that RPM-1 is positioned to potentially coordinate the construction of synapses with regulation of axon extension and termination.
(Source: scripps.edu)
Glitch in garbage removal enhances risk
An international team of researchers identified a pathogenic mechanism that is common to several neurodegenerative diseases. The findings suggest that it may be possible to slow the progression of dementia even after the onset of symptoms.
The relentless increase in the incidence of dementia in aging societies poses an enormous challenge to health-care systems. An international team of researchers led by Professor Christian Haass and Gernot Kleinberger at the LMU‘s Adolf-Butenandt-Institute and the German Center for Neurodegenerative Diseases (DZNE), has now elucidated the mode of action of a genetic defect that contributes to the development of several different dementia syndromes.
Neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases or frontotemporal dementia display a number of common features. They are all characterized by the appearance in the brains of affected patients of abnormally high levels of insoluble protein deposits, which are associated with massive loss of nerve cells. In order to minimize further damage to nerve cells in the vicinity of such deposits, dead cells and the proteinaceous aggregates released from them must be efficiently degraded and disposed of. This task is performed by specialized phagocytic cells – the so-called microglia – which act as “sanitary inspectors” in the brain to ensure the prompt removal of debris that presents a danger to the health of nearby cells. Microglia are found only in the central nervous system, but functionally they represent a division of the body’s innate immune system.
As Haass and his colleagues now report in the latest issue of the journal Science Translational Medicine, specific mutations in the gene for a protein called TREM2, which regulates the uptake of waste products by microglia, lead to its absence from the cell surface. TREM2 is normally inserted into the plasma membrane of microglial cells such that part of it extends through the membrane as an extracellular domain. This exposed portion of TREM2 is responsible for the recognition of waste products left behind by dead cells. “We believe that the genetic defect disrupts the folding of the protein chain soon during its synthesis in the cell, so that it is degraded before it can reach the surface of the microglia,” says Kleinberger. As a result, the amount of debris that the microglia can cope with is significantly reduced. Consequently, the toxic protein deposits, as well as whole dead cells, cannot be efficiently removed and continue to accumulate in the brain. This is expected to trigger inflammatory reactions that may promote further nerve-cell loss.
The new study thus pinpoints a mechanism that influences the course of several different brain diseases. “In addition, our findings may perhaps point to ways of slowing the rate of progression of these illnesses even after the manifestation of overt signs of dementia, which has not been possible so far,” says Haass. “That this may indeed be feasible is suggested by the initial results of an experiment in which we were able to stimulate the phagocytic activity of microglia by pharmacological means.”
(Source: en.uni-muenchen.de)
Do not disturb! How the brain filters out distractions
You know the feeling? You are trying to dial a phone number from memory… you have to concentrate…. then someone starts shouting out other numbers nearby. In a situation like that, your brain must ignore the distraction as best it can so as not to lose vital information from its working memory. A new paper published in Neuron by a team of neurobiologists led by Professor Andreas Nieder at the University of Tübingen gives insight into just how the brain manages this problem.
The researchers put rhesus monkey in a similar situation. The monkeys had to remember the number of dots in an image and reproduce the knowledge a moment later. While they were taking in the information, a distraction was introduced, showing a different number of dots. And even though the monkeys were mostly able to ignore the distraction, their concentration was disturbed and their memory performance suffered.
Measurements of the electrical activity of nerve cells in two key areas of the brain showed a surprising result: nerve cells in the prefrontal cortex signaled the distraction while it was being presented, but immediately restored the remembered information (the number of dots) once the distraction was switched off. In contrast, nerve cells in the parietal cortex were unimpressed by the distraction and reliably transmitted the information about the correct number of dots.
These findings provide important clues about the strategies and division of labor among different parts of the brain when it comes to using the working memory. “Different parts of the brain appear to use different strategies to filter out distractions,” says Dr. Simon Jacob, who carried out research in Tübingen before switching to the Psychiatric Clinic at the Charité hospitals in Berlin. “Nerve cells in the parietal cortex simply suppress the distraction, while nerve cells in the prefrontal cortex allow themselves to be momentarily distracted – only to return immediately to the truly important memory content.”
The researchers were surprised by the two brain areas’ difference in sensitivity to distraction. “We had assumed that the prefrontal cortex is able to filter out all kinds of distractions, while the parietal cortex was considered more vulnerable to disturbances,” says Professor Nieder. “We will have to rethink that. The memory-storage tasks and the strategies of each brain area are distributed differently from what we expected.”
Researchers discover a “switch” in Alzheimer’s and stroke patient brains
A new study by researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) has identified a chemical “switch” that controls both the generation of new neurons from neural stem cells and the survival of existing nerve cells in the brain. The switch that shuts off the signals that promote neuron production and survival is in abundance in the brains of Alzheimer’s patients and stroke victims. The study, published July 3 in Cell Reports, suggests that chemical switch, MEF2, may be a potential therapeutic target to protect against neuronal loss in a variety of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and autism.
“We have shown that when nitric oxide (NO)—a highly reactive free radical—reacts with MEF2, MEF2 can no longer bind to and activate the genes that drive neurogenesis and neuronal survival,” said Stuart Lipton, M.D., Ph.D., director and professor in the Neuroscience and Aging Research Center at Sanford-Burnham, and a practicing clinical neurologist. “What’s unique here is that a single alteration to MEF2 controls two distinct events—the generation of new neurons and the survival of existing neurons,” added Lipton, who is senior author of the study.
In the brain, transcription factors are critical for linking external stimuli to protein production, enabling neurons to adapt to changing environments. Members of the MEF2 family of transcription factors have been shown to play an important role in neurogenesis and neuronal survival, as well as in the processes of learning and memory. And, mutations of the MEF2 gene have been associated with a range of neurodegenerative disorders, including Alzheimer’s and autism.
The process of NO-protein modifications—known as S-nitrosylation—was first described by Lipton and collaborators some 20 years ago. S-nitrosylation has important regulatory functions under normal physiological conditions throughout the body. However, with aging, environmental toxins, or stress-related injuries, abnormal S-nitrosylation reactions can occur, contributing to disease pathogenesis.
“Our laboratory had previously shown that S-nitrosylation of MEF2 controlled neuronal survival in Parkinson’s disease,” said Lipton. “Now we have shown that this same reaction is more ubiquitous, occurring in other neurological conditions such as stroke and Alzheimer’s disease. While the major gene targets of MEF2 may be different in various diseases and brain areas, the remarkable new finding here is that we may be able to treat each of these neurological disorders by preventing a common S-nitrosylation modification to MEF2.
“The findings suggest that the development of a small therapeutic molecule—one that can cross the blood-brain barrier and block S-nitrosylation of MEF2 or in some other way increase MEF2 transcriptional activity—could promote new brain cell growth and protect existing cells in several neurodegenerative disorders,” added Lipton.
“We have already found several such molecules in our high-throughput screening and drug discovery efforts, so the potential for developing new drugs to attack this pathway is very exciting,” said Lipton.