Degenerative Diseases

Unraveling the molecular roots of Down syndrome

by Heather Buschman, Ph.D. on March 24, 2013 at 11:00 am | 29 Comments

Neurons from a normal mouse (left) are longer and fuller than neurons from a mouse lacking SNX27 (right).

Researchers discover that the extra chromosome inherited in Down syndrome impairs learning and memory because it leads to low levels of SNX27 protein in the brain.

What is it about the extra chromosome inherited in Down syndrome—chromosome 21—that alters brain and body development? Researchers have new evidence that points to a protein called sorting nexin 27, or SNX27. SNX27 production is inhibited by a molecule encoded on chromosome 21. The study, published March 24 in Nature Medicine, shows that SNX27 is reduced in human Down syndrome brains. The extra copy of chromosome 21 means a person with Down syndrome produces less SNX27 protein, which in turn disrupts brain function. What’s more, the researchers showed that restoring SNX27 in Down syndrome mice improves cognitive function and behavior.

Chemical reaction keeps stroke-damaged brain from repairing itself

by Heather Buschman, Ph.D. on February 4, 2013 at 12:01 pm | 2 Comments

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Neuron

In stroke and other neurological disorders, nitric oxide damages neurons and blocks the brain’s ability to self-repair

Nitric oxide, a gaseous molecule produced in the brain, can damage neurons. When the brain produces too much nitric oxide, it contributes to the severity and progression of stroke and neurodegenerative diseases such as Alzheimer’s. Researchers at Sanford-Burnham Medical Research Institute recently discovered that nitric oxide not only damages neurons, it also shuts down the brain’s repair mechanisms. Their study was published February 4 by the Proceedings of the National Academy of Sciences.

“In this study, we’ve uncovered new clues as to how natural chemical reactions in the brain can contribute to brain damage—loss of memory and cognitive function—in a number of diseases,” said Stuart A. Lipton, M.D., Ph.D., director of Sanford-Burnham’s Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research and a clinical neurologist.

Lipton led the study, along with Sanford-Burnham’s Tomohiro Nakamura, Ph.D., who added that these new molecular clues are important because “we might be able to develop a new strategy for treating stroke and other disorders if we can find a way to reverse nitric oxide’s effect on a particular enzyme in nerve cells.”

Neurons made from stem cells drive brain activity after transplantation in laboratory model

Originally published November 15, 2012

Researchers and patients look forward to the day when stem cells might be used to replace dying brain cells in Alzheimer’s disease and other neurodegenerative conditions. Scientists are currently able to make neurons and other brain cells from stem cells, but getting these neurons to properly function when transplanted to the host has proven to be more difficult. Now, researchers at Sanford-Burnham Medical Research Institute have found a way to stimulate stem cell-derived neurons to direct cognitive function after transplantation to an existing neural network. The study was published November 7 in the Journal of Neuroscience.

Transplanted neural stem cells treat ALS in mouse model

by Heather Buschman, Ph.D. on December 19, 2012 at 11:00 am | 1 comment

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A consortium of researchers around the U.S. used transplanted neural stem cells (shown here) to treat a mouse model of ALS.

In 11 independent studies, a consortium of ALS researchers shows that transplanting neural stem cells into the spinal cord of an ALS mouse model slows disease onset and progression, improves motor function, and significantly prolongs survival.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is untreatable and fatal. Nerve cells in the spinal cord die, eventually taking away a person’s ability to move or even breathe. A consortium of ALS researchers at multiple institutions, including Sanford-Burnham Medical Research Institute, Brigham and Women’s Hospital, and the University of Massachusetts Medical School, tested transplanted neural stem cells as a treatment for the disease. In 11 independent studies, they found that transplanting neural stem cells into the spinal cord of a mouse model of ALS slows disease onset and progression. This treatment also improves host motor function and significantly prolongs survival.

Surprisingly, the transplanted neural stem cells did not benefit ALS mice by replacing deteriorating nerve cells. Instead, neural stem cells help by producing factors that preserve the health and function of the host’s remaining nerve cells. They also reduce inflammation and suppress the number of disease-causing cells in the host’s spinal cord. These findings, published December 19 in Science Translational Medicine, demonstrate the potential neural stem cells hold for treating ALS and other nervous system disorders.

“While not a cure for human ALS, we believe that the careful transplantation of neural stem cells, particularly into areas that can best sustain life—respiratory control centers, for example—may be ready for clinical trials,” Evan Y. Snyder, M.D., Ph.D., director of Sanford-Burnham’s Stem Cell and Regenerative Biology Program and senior author of the study.

Compound found in rosemary protects against macular degeneration in laboratory model

by Heather Buschman, Ph.D. on November 27, 2012 at 12:01 pm | 3 Comments

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Left: Control cells exposed to hydrogen peroxide. Right: Cells treated with carnosic acid are protected from hydrogen peroxide. Live cells are stained green, dead cells are stained red.

Researchers discover that carnosic acid, a component of the herb rosemary, promotes eye health in rodents—providing a possible new approach for treating conditions such as age-related macular degeneration.

Herbs widely used throughout history in Asian and early European cultures have received renewed attention by Western medicine in recent years. Scientists are now isolating the active compounds in many medicinal herbs and documenting their antioxidant and anti-inflammatory activities. In a study published in the journal Investigative Ophthalmology & Visual Science, Stuart A. Lipton, M.D., Ph.D. and colleagues at Sanford-Burnham Medical Research Institute report that carnosic acid, a component of the herb rosemary, promotes eye health.

Lipton’s team found that carnosic acid protects retinas from degeneration and toxicity in cell culture and in rodent models of light-induced retinal damage. Their findings suggest that carnosic acid may have clinical applications for diseases affecting the outer retina, including age-related macular degeneration, the most common eye disease in the U.S.

Neurons made from stem cells drive brain activity after transplantation in laboratory model

by Heather Buschman, Ph.D. on November 15, 2012 at 11:28 am | 4 Comments

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Stuart A. Lipton, M.D., Ph.D., director of Sanford-Burnham’s Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research and a clinical neurologist

Sanford-Burnham researchers convince transplanted stem cell-derived neurons to direct cognitive function—getting us a step closer to using these cells to treat Alzheimer’s disease and other neurodegenerative conditions.

Searching for causes of neuron death in Alzheimer’s and TBI

by Heather Buschman, Ph.D. on November 8, 2012 at 5:26 am | 6 Comments

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In Alzheimer's and traumatic brain injury, neurons (red) are killed off by the protein appoptosin

Sanford-Burnham researchers discovered that the protein appoptosin prompts neurons to commit suicide in several neurological conditions—giving them a new therapeutic target for Alzheimer’s disease and traumatic brain injury.

Dying neurons lead to cognitive impairment and memory loss in patients with neurodegenerative disorders–conditions like Alzheimer’s disease and traumatic brain injury. To better diagnose and treat these neurological conditions, scientists first need to better understand the underlying causes of neuronal death.

Enter Huaxi Xu, Ph.D., professor in Sanford-Burnham’s Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research. He and his team have been studying the protein appoptosin and its role in neurodegenerative disorders for the past several years. Appoptosin levels in the brain skyrocket in conditions like Alzheimer’s and stroke, and especially following traumatic brain injury.

Appoptosin is known for its role in helping the body make heme, the molecule that carries iron in our blood (think “hemoglobin,” which makes blood red). But what does heme have to do with dying brain cells? As Xu and his group explain in a paper they published recently in the Journal of Neuroscience, excess heme leads to the overproduction of reactive oxygen species, which include cell-damaging free radicals and peroxides, and triggers apoptosis, the carefully regulated process of cellular suicide. This means that more appoptosin and more heme cause neurons to die.

MS patients and researchers inspire one another

by Heather Buschman, Ph.D. on October 22, 2012 at 3:13 pm | 0 Comments

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Dr. Barbara Ranscht (second from left), with National MS Society staff - Karen Hooper, Richard Israel, and Dr. Zuzana Hostomska

The National Multiple Sclerosis Society—a group including patients, donors, and Society leaders—recently came out to meet Sanford-Burnham’s Barbara Ranscht, Ph.D., tour her lab, and learn how she and her team are laying the groundwork for future Multiple Sclerosis (MS) therapies.

In MS, a person’s immune system mistakes myelin—the protective coating around nerve fibers in the brain—for a foreign substance and attacks it. As a result, these fibers, called axons, become vulnerable and prone to inducing neurodegeneration and cell death. Ultimately, the brain has trouble telling the rest of the body what to do.

“Myelin is necessary for rapid nerve impulse conduction—those times when you need a quick reaction, like pulling your hand off a hot burner,” Ranscht explained in her talk. “It’s also needed to protect the axons and ensure the health of our neurons.”

Symptoms of MS can be mild, such as numbness in the arms and legs, or severe, causing paralysis, vision loss, or other impairments. Severity and progression vary widely from one individual to another. Approximately 400,000 people in the U.S. are living with MS.

“Many of these MS patients often visit medical clinics to see their doctors and receive treatment, but it’s not often that they get to hear about the science behind it all—what researchers are learning about the disease and what new therapeutic approaches might be coming down the pipeline,” said Richard Israel, president of the Pacific South Coast Chapter of the National MS Society.

Stem cells 101

by Communications Staff on October 8, 2012 at 10:52 am | 2 Comments

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Sanford-Burnham's Stem Cell Research Center

Congratulations to John B. Gurdon and Shinya Yamanaka on winning the 2012 Nobel Prize in Physiology or Medicine! They received the award today for their “discovery that mature cells can be reprogrammed to become pluripotent.” In other words, these scientists figured out how to turn a normal adult cell, such as a skin cell, into a stem cell that has the potential to become any other type of cell in the body. Read below to learn more about stem cells and how they are revolutionizing medical research.

What are stem cells?

Stem cells are special because each is like a blank slate. Once it’s given the proper instruction, a stem cell can specialize and become any type of cell in the body—brain, heart, muscle, and more. Stem cells also have the ability to reproduce themselves indefinitely, renewing the supply.

Are there different types of stem cells?

Embryonic stem cells only exist during an organism’s development, when it is an embryo. These cells are pluripotent, meaning they have the capacity to become any cell type in the body.

Adult stem cells exist in fully developed organisms. They are more limited than embryonic stem cells—they are multipotent rather than pluripotent. These stem cells usually can only become a few types of specialized cells, based on the tissue from which they originate.

Induced pluripotent stem cells (iPSCs) are pluripotent, much like embryonic stem cells. iPSCs are produced in the laboratory by genetically reprogramming any adult cell, such as a skin cell.

Brain enzyme is double whammy for Alzheimer’s disease

by Heather Buschman, Ph.D. on August 17, 2012 at 2:44 pm | 2 Comments

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Beta-amyloid plaques (red) and a tangle (black, lower right) in the brain of an Alzheimer's patient.

The underlying causes of Alzheimer’s disease are not fully understood, but a good deal of evidence points to the accumulation of β-amyloid, a protein that’s toxic to nerve cells. β-amyloid is formed by the activity of several enzymes, including one called BACE1. Most Alzheimer’s disease patients have elevated levels of BACE1, which in turn leads to more brain-damaging β-amyloid protein. In a paper published August 15 in The Journal of Neuroscience, Sanford-Burnham researchers found that BACE1 does more than just help produce β-amyloid—it also regulates another cellular process that contributes to memory loss. This means that just inhibiting BACE1’s enzymatic activity as a means to prevent or treat Alzheimer’s disease isn’t enough—researchers will have to prevent cells from making it at all.

“Memory loss is a big problem—not just in Alzheimer’s disease, but also in the normal aging population,” said Huaxi Xu, Ph.D., professor in Sanford-Burnham’s Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research and senior author of the study. “In this study, we wanted to better understand how BACE1 plays a role in memory loss, apart from β-amyloid production.”

Disarming the botulinum neurotoxin

by Heather Buschman, Ph.D. on February 23, 2012 at 11:01 am | 1 comment

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Rongsheng Jin, Ph.D., assistant professor at Sanford-Burnham

Researchers at Sanford-Burnham Medical Research Institute and collaborators at the Medical School of Hannover in Germany recently discovered how the botulinum neurotoxin, a potential bioterrorism agent, survives the hostile environment in the stomach on its journey through the human body. Their study, published February 24 in Science, reveals the first 3D structure of a neurotoxin together with its bodyguard, a protein made simultaneously in the same bacterium. The bodyguard keeps the toxin safe through the gut, then lets go as the toxin enters the bloodstream. This new information also reveals the toxin’s weak spot—a point in the process that can be targeted with new therapeutics.

“Now that we better understand the structure of the bacterial machinery that was designed for highly efficient toxin protection and delivery, we can see more clearly how to break it,” said Rongsheng Jin, Ph.D., assistant professor in Sanford-Burnham’s Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research and senior author of the study.

Unusual alliances enable movement

by Guest Blogger on February 9, 2012 at 6:57 am | 1 comment

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Rongsheng Jin, Ph.D (second from the right) and researchers in his laboratory

provided by Georgia Health Sciences University

Some unusual alliances are necessary for you to wiggle your fingers, researchers report.

Understanding those relationships should enable better treatment of neuromuscular diseases, such as myasthenia gravis, which prevent muscles from taking orders from your brain, said Lin Mei, Ph.D., director of the Institute of Molecular Medicine and Genetics at Georgia Health Sciences University.

During development, neurons in the spinal cord reach out to muscle fibers to form a direct line of communication called the neuromuscular junction. Once complete, motor neurons send chemical messengers, called acetylcholine, via that junction so you can text, walk, or breathe.

Two Sanford-Burnham researchers named AAAS Fellows

by Communications Staff on December 23, 2011 at 6:00 am | 0 Comments

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Dr. John Reed and Dr. Stuart Lipton

Sanford-Burnham is a highly collaborative institute, embracing opportunities to connect with scientists nationwide, so perhaps the greatest honor our researchers can receive is the recognition of their peers. Our CEO John C. Reed, M.D., Ph.D., and Director of our Del E. Webb Neuroscience, Aging and Stem Cell Research Center, Stuart A. Lipton, M.D., Ph.D., have been named as Fellows of the American Association for the Advancement of Science (AAAS). Fellows are recognized for meritorious efforts to advance science or its applications. This year’s honorees were formally announced today in the AAAS News & Notes section of the journal Science.

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Using stem cells to treat Parkinson’s disease

by Heather Buschman, Ph.D. on September 26, 2011 at 7:13 am | 1 comment

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Neurons derived from embryonic stem cells

When neurons that make a chemical called dopamine are slowly destroyed, nerve cells in that part of the brain cannot properly send the messages that would normally control muscle function. As the damage gets worse with time, a person experiences tremors and movement becomes difficult. This is Parkinson’s disease.

In short, Parkinson’s patients need more dopamine. Or, better yet, new neurons that produce dopamine on their own. In a paper published August 25 in the journal PLoS ONE, a team led by Dr. Stuart Lipton, director of Sanford-Burnham’s Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research, demonstrates how this therapeutic approach might be possible.

Autophagy 101

by Bruce Lieberman on September 5, 2011 at 7:34 am | 0 Comments

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An autophagosome full of degraded old cell parts, as viewed under an electron microscope. (Image by Malcolm Woods, The Scripps Research Institute)

Every well-run house needs someone to clean up the clutter, prune the hedges, and rake up the leaves, even whip up something to eat when the refrigerator is empty. In the life of a cell, those kinds of jobs are handled by an incredible process called autophagy.

Biologists first observed autophagy in the early 1960s as a mechanism by which cells break down their own components and recycle the parts. Autophagy, which literally means “to eat oneself,” is essential to cell survival, particularly when food is scarce.

But there’s a much larger role for autophagy than just helping a cell survive starvation. The process helps cells dispose of malfunctioning parts, clean up clutter, and defend against invading pathogens.

Top Stories - Degenerative Diseases

Unraveling the molecular roots of Down syndrome

Chemical reaction keeps stroke-damaged brain from repairing itself

Top 10 most-read blog posts of 2012: #8

Neurons made from stem cells drive brain activity after transplantation in laboratory model

Transplanted neural stem cells treat ALS in mouse model

Compound found in rosemary protects against macular degeneration in laboratory model

Neurons made from stem cells drive brain activity after transplantation in laboratory model

Searching for causes of neuron death in Alzheimer’s and TBI

MS patients and researchers inspire one another

Stem cells 101

What are stem cells?

Are there different types of stem cells?

Read More

Brain enzyme is double whammy for Alzheimer’s disease

Disarming the botulinum neurotoxin

Unusual alliances enable movement

Two Sanford-Burnham researchers named AAAS Fellows

Using stem cells to treat Parkinson’s disease

Autophagy 101

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Neurons made from stem cells drive brain activity after transplantation in laboratory model

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