Alzheimer’s disease

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.

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

Full Article

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

Full Article

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.

Stem cells 101

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

Full Article

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

Full Article

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.”

How to make new neurons

by Bruce Lieberman on August 31, 2011 at 9:55 am | 0 Comments

Full Article

Neurons (Image courtesy of the Lipton lab)

Imagine the ability to take skin cells from a patient with Alzheimer’s disease, convert them directly into brain cells, and then study how the disease progresses in those cells—which still contain the patient’s DNA—all in the lab, with minimal invasiveness on the part of the patient. Then imagine taking those same brain cells and testing novel but risky drugs that could cure the devastating disease—again, in the safety of a dish in the lab.

Researchers are on their way to achieving this remarkable milestone. Dr. Stuart Lipton at Sanford-Burnham, Dr. Sheng Ding at the Gladstone Institutes, and their collaborators recently figured out how to reprogram skin cells directly into functioning neurons. The study was published online July 28 in the journal Cell Stem Cell.

“This technology should allow us to very rapidly model neurodegenerative diseases in a dish by making nerve cells from individual patients in just a matter of days, rather than the months required previously,” Dr. Lipton says in a statement released by the Gladstone Institutes.

The paper is one of several recent studies that are all zeroing in on a long-sought-after advance in stem cell science: the potential to obtain unlimited numbers of brain cells from an easily accessible tissue such as the skin.

A scientist’s life: 10 things Carl Ware has done

by Heather Buschman, Ph.D. on August 26, 2011 at 11:42 am | 0 Comments

Full Article

Dr. Carl Ware (Photo by Nadia Borowski Scott)

Meet Dr. Carl Ware, director of our Infectious and Inflammatory Disease Center. The San Diego Union-Tribune gives us a glimpse of what he has experienced throughout his life: surfing, hitchhiking, meeting Chuck Berry … and Alzheimer’s disease.

Read A Scientist’s Life: 10 Things Carl Ware Has Done.

Developments to Watch: New frontier in Alzheimer’s disease

by Communications Staff on August 24, 2011 at 10:26 am | 0 Comments

Full Article

Dr. Evan Snyder (right) interviews Dr. Stuart Lipton in Medscape's "Developments to Watch"

Medscape, a physician-oriented website run by WebMD, visited Sanford-Burnham’s La Jolla campus this summer to record interviews with researchers from both Orlando and San Diego for a new online video program called Developments to Watch. The talk show-like discussions are hosted by Dr. Evan Snyder, who directs the Stem Cells and Regenerative Biology Program at Sanford-Burnham. The first episode, A New Frontier in Alzheimer’s Disease, is now available. In the video, Dr. Snyder speaks with Dr. Stuart Lipton, director of the Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research, about his work on Alzheimer’s disease. They discuss what new findings—and potential treatments—are on the horizon and how they might impact patients.

A user name and password are required to access Medscape, but the site and content are free. New installments will be added monthly.

Watch the video, then come back here to let us know what you think!

For more about our research on Alzheimer’s disease, check out these blog posts:
Getting to the root of Alzheimer’s disease
Diagnosing Alzheimer’s Earlier
New Partnership Targets Brain Conditions
Safely Treating Alzheimer’s Disease
Saying NO to Alzheimer’s and Parkinson’s Diseases

Getting to the root of Alzheimer’s disease

by Heather Buschman, Ph.D. on August 17, 2011 at 5:47 am | 0 Comments

Full Article

Dr. Stuart Lipton

Alzheimer’s disease is characterized by abnormal proteins that stick together in little globs, disrupting cognitive function (thinking, learning, and memory). These sticky proteins are mostly made up of beta-amyloid peptide. A better understanding of these proteins, how they form, and how they affect brain function will no doubt improve the diagnosis and treatment of Alzheimer’s disease.

To this end, a research team led by Dr. Stuart Lipton‘s group found that beta-amyloid-induced destruction of synapses—the connections that mediate communication between nerve cells—is driven by a chemical modification to an enzyme called Cdk5. The team found that this altered form of Cdk5 (SNO-Cdk5) was prevalent in human Alzheimer’s disease brains, but not in normal brains. These results, published August 15 in the Proceedings of the National Academy of Sciences of the USA, suggest that SNO-Cdk5 could be targeted for the development of new Alzheimer’s disease therapies.

Cdk5 is an enzyme known to play a role in normal neuronal survival and migration. In this study, Dr. Lipton and colleagues found that beta-amyloid peptides, the hallmark of Alzheimer’s disease, trigger Cdk5 modification by a chemical process called S-nitrosylation. In this reaction, nitric oxide (NO) is attached to the enzyme, producing SNO-Cdk5 and disrupting its normal activity.

Join us for a congressional briefing on Alzheimer’s disease

by Heather Buschman, Ph.D. on July 8, 2011 at 3:25 pm | 1 comment

Full Article

The United States Capitol, Washington, D.C.

What: Congressional Briefing on Alzheimer’s Disease Research and Therapeutic Advancements, Innovations and Treatments

CHI-The California Healthcare Institute and the Healthcare Institute of New Jersey (HINJ) invite you to a congressional briefing that will facilitate a dialogue about Alzheimer’s disease research. This program will include an overview of advances stemming from California’s and New Jersey’s life sciences sectors, with an expert panel discussing current research and drug development, as well as future discoveries, followed by a brief question and answer session.

When: July 14, 2011, 9:30 a.m. – 11 a.m.
Where: Capitol Visitor’s Center, Congressional Meeting Room South, Washington, D.C.

Why: According to a 2011 report released by the Alzheimer’s Association, an estimated 5.4 million people are living with Alzheimer’s disease, and someone develops the disease every 69 seconds. The United States, like many other countries, has an aging population with nearly one in five residents reaching the age of 65 or older by 2030. Additionally, in 2010, 14.9 million family members and friends provided 17 billion hours of unpaid care to those living with Alzheimer’s and other dementias — care valued at approximately $202 billion. With the imminent increase in dementia caused by Alzheimer’s disease and other conditions — and without a cure — the development of new innovations and treatments remains all the more critical to assist in improving the quality of life for those affected. CHI members Genentech, Pfizer, Sanford-Burnham and University of California, Irvine and HINJ members Merck, Lundbeck, Bayer and Pfizer are all working to advance important new studies and therapeutics.

Who:
Rep. Chris Smith (R-NJ)
Rep. Linda Sanchez (D-CA)

David Gollaher, Ph.D., President & CEO, CHI
Dean J. Paranicas, President & CEO, HealthCare Institute of New Jersey (HINJ)
Joseph Hammang, Ph.D., Senior Director, Worldwide Science Policy, Pfizer
Stuart Lipton, M.D., Ph.D., Director, Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical Research Institute
Bob Nelson, Ph.D., Research Fellow, Lundbeck Research USA
Wayne Poon, Ph.D., Director, UCI MIND Brain Bank and Tissue Repository
Kimberly Scearce-Levie, Ph.D., head of in vivo neurobiology at Genentech Inc.

RSVP to Caitlin Doyle at doyle@chi.org or (202) 974-6323

Diagnosing Alzheimer’s Earlier

by Amelia Tomas on April 27, 2011 at 9:59 am | 0 Comments

Full Article

Dr. Stuart Lipton

For the first time in nearly 30 years, new criteria will guide the diagnosis of Alzheimer’s disease. The current approach focuses on an individual’s cognitive decline – primarily thinking, learning and memory. But new research has shown that changes in the brain happen long before these symptoms emerge, perhaps even decades earlier.

The new guidelines, issued in April by the National Institute on Aging and the Alzheimer’s Association, spotlight the disease’s progression from its earliest onset (molecular changes in the brain). The goal is to detect the disease faster in at-risk patients. As research advances, these new diagnostic tools could allow doctors to treat patients proactively to prevent the emergence of physical symptoms.

“These guidelines should help us diagnose Alzheimer’s earlier, which eventually will be very important as new treatments for early intervention are developed,” stated Dr. Stuart Lipton, director of Sanford-Burnham’s Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research. Dr. Lipton is also a neurologist who sees many Alzheimer’s disease patients in his own clinical practice and is credited with developing memantine (marketed in the United States as Namenda®), the latest FDA-approved Alzheimer’s drug.

Safely Treating Alzheimer’s Disease

by Heather Buschman, Ph.D. on August 18, 2010 at 1:31 pm | 7 Comments

Full Article

Alzheimer’s disease is a neurodegenerative condition – nerve cells and their connections are destroyed, interrupting a person’s memory, thinking skills and ability to perform daily tasks. Dr. Stuart Lipton, director of Sanford-Burnham’s Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research, was part of a team that developed memantine, a drug approved by the FDA to alleviate the symptoms of moderate-to-severe Alzheimer’s disease.

Memantine (marketed in the United States as Namenda®) improves symptoms by blocking abnormal activity of glutamate, a chemical that transmits messages between nerve cells. Recently in The Journal of Neuroscience, a team of investigators at Sanford-Burnham led by Dr. Lipton and post-doctoral researcher Dr. Peng Xia reveal exactly how memantine helps Alzheimer’s patients without causing serious side effects.

“While memantine is partially effective in treating Alzheimer’s disease, one of its major advantages is how safe and well-tolerated it is clinically,” Dr. Lipton said.

Saying NO to Alzheimer’s and Parkinson’s Diseases

by Heather Buschman, Ph.D. on July 30, 2010 at 12:32 pm | 2 Comments

Full Article

Dr. Tomohiro Nakamura

Neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s disease all have one thing in common: the untimely death of nerve cells. New research at Sanford-Burnham shows that these diseases also share the molecular mechanism that leads to cellular death, a finding that identifies new targets for diagnosis and treatment of these diseases. The study, which appeared in today’s issue of Molecular Cell, was led by Dr. Stuart Lipton, director of Sanford-Burnham’s Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research, and Dr. Tomohiro Nakamura, research assistant professor.Together with their collaborators, Drs. Lipton and Nakamura showed how a gaseous molecule known as nitric oxide (NO) can throw a molecular switch to turn a cell from the path to survival to the path to death.

Scientists have long known that under certain conditions, NO binds to and reacts with caspases, a series of enzymes that are important in cell death. When NO interacts with caspases in this way, it inhibits their activity and prevents nerve cells from dying. But in an entirely unexpected way, the Sanford-Burnham team has now found that an inhibitor of caspases – called XIAP – can also bind to NO. In a process known as transnitrosylation, NO jumps like a “hot potato” from caspases to XIAP. The hot potato inhibits XIAP function, which would normally turn off caspases.

“It’s a double whammy – caspases are activated when NO leaves, but when NO binds XIAP, it also blocks the brake on caspases,” Dr. Lipton explained. “And cells enter the death pathway.”

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

Neurons made from stem cells drive brain activity after transplantation 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

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

How to make new neurons

A scientist’s life: 10 things Carl Ware has done

Developments to Watch: New frontier in Alzheimer’s disease

Getting to the root of Alzheimer’s disease

Join us for a congressional briefing on Alzheimer’s disease

Diagnosing Alzheimer’s Earlier

Safely Treating Alzheimer’s Disease

Saying NO to Alzheimer’s and Parkinson’s Diseases

Search

Find more information

Please take a quick survey

Which of these items describes you?

Categories

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

What are stem cells?

Are there different types of stem cells?

Search

Find more information

Please take a quick survey

Which of these items describes you?

Categories

Search by Keyword