(Press-News.org) 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 Neuroscience, Aging, and Stem Cell Research Center. 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 October 31 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.
Not only did Xu and his team unravel this whole appoptosin-heme-neurodegeneration mechanism, but when they inhibited appoptosin in laboratory cell cultures, they noticed that the cells didn't die. This finding suggests that appoptosin might make an interesting new therapeutic target for neurodegenerative disorders.
What's next? Xu and colleagues are now probing appoptosin's function in mouse models. They're also looking for new therapies that target the protein.
"Since the upregulation of appoptosin is important for cell death in diseases such as Alzheimer's, we're now searching for small molecules that modulate appoptosin expression or activity. We'll then determine whether these compounds may be potential drugs for Alzheimer's or other neurodegenerative diseases," Xu explains.
Putting a stop to runaway appoptosin won't be easy, though. That's because we still need the heme-building protein to operate at normal levels for our blood to carry iron. In a previous study, researchers found that a mutation in the gene that encodes appoptosin causes anemia. "Too much of anything is bad, but so is too little," Xu says.
New therapies that target neurodegenerative disorders and traumatic brain injury are sorely needed. According to the CDC, approximately 1.7 million people sustain a traumatic brain injury each year. It's an acute injury, but one that can also lead to long-term problems, causing epilepsy and increasing a person's risk for Alzheimer's and Parkinson's diseases. Not only has traumatic brain injury become a worrisome problem in youth and professional sports in recent years, the Department of Defense calls traumatic brain injury "one of the signature injuries of troops wounded in Afghanistan and Iraq."
###
This study was funded by the U.S. National Institutes of Health (National Institute on Aging grants R01AG038710, R01AG021173, R01AG030197, R03AG034366, R01AG031893, AG5131, AG18440, R21AG038968; National Institute of Neurological Disorders and Stroke grants R01NS046673, R01NS054880) and the Alzheimer's Association.
Original paper:
Zhang H, Zhang YW, Chen Y, Huang X, Zhou F, Wang W, Xian B, Zhang X, Masliah E, Chen Q, Han JD, Bu G, Reed JC, Liao FF, Chen YG, & Xu H (2012). Appoptosin is a Novel Pro-Apoptotic Protein and Mediates Cell Death in Neurodegeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience, 32 (44), 15565-15576 PMID: 23115192
About Sanford-Burnham Medical Research Institute
Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. The Institute consistently ranks among the top five organizations worldwide for its scientific impact in the fields of biology and biochemistry (defined by citations per publication) and currently ranks third in the nation in NIH funding among all laboratory-based research institutes. Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a U.S.-based, non-profit public benefit corporation, with operations in San Diego (La Jolla), California and Orlando (Lake Nona), Florida. For more information, news, and events, please visit us at sanfordburnham.org.
Hunting neuron killers in Alzheimer's and TBI
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
2012-11-09
ELSE PRESS RELEASES FROM THIS DATE:
How infection can trigger autoimmune disease
2012-11-09
Australian scientists have confirmed a 'weak link' in the immune system – identifying the exact conditions under which an infection can trigger an autoantibody response, a process not clearly understood until now.
We have known for many years that autoimmune diseases such as rheumatic fever and Guillain-Barré syndrome (where the body makes antibodies that attack the heart and peripheral nerves respectively) can occur after the body makes immune responses against certain infectious micro-organisms.
We have not been able to explain exactly how such examples of infection-driven ...
High capacity vehicles the future?
2012-11-09
AWARD-winning research by a transport and logistics expert at the University of Huddersfield has shown that there would be economic and environmental benefits to individual companies and the country if the UK changed the rules to allow high capacity vehicles (HCVs) on to its roads.
At 25.25 metres, they would be around a third as long again as the largest lorries currently permitted in Britain. But they would NOT carry heavier loads. They would be used for larger quantities of lightweight goods, therefore cutting down the number of vehicle journeys made, leading to ...
A new way of making glass
2012-11-09
When cooling a liquid below its melting temperature it either crystallizes or transforms into a glass. Glass is a peculiar state of matter: it has the mechanical properties of a solid but an amorphous structure like a liquid.
As long ago as 1952, Sir Charles Frank at the University of Bristol argued that the structure of glasses should not be entirely disordered like a liquid but rather that it should be filled with polyhedra like the bicapped square antiprism.
Although such motifs have very recently been found in experiments and computer simulations on glassy materials, ...
Super storm tracked by European Space Agency water mission
2012-11-09
When millions of people are bracing themselves for the onslaught of extreme weather, as much information as possible is needed to predict the strength of the impending storm. ESA's SMOS mission again showed its versatility by capturing unique measurements of Hurricane Sandy.
As its name suggests, the Soil Moisture and Ocean Salinity (SMOS) satellite was designed to measure how much moisture is held in soil and how much salt is held in the surface waters of the oceans.
This information is helping to improve our understanding of the water cycle – an essential component ...
A scientific explanation to why people perform better after receiving a compliment
2012-11-09
A team of Japanese scientists have found scientific proof that people doing exercises appear to perform better when another person compliments them. The research was carried out by a group lead by National Institute for Physiological Sciences Professor Norihiro Sadato, Graduate University for Advanced Studies graduate student Sho Sugawara, Nagoya Institute of Technology Tenure-Track Associate Professor Satoshi Tanaka, and in collaboration with Research Center for Advanced Science and Technology Associate Professor Katsumi Watanabe. The team had previously discovered that ...
Understanding antibiotic resistance using crystallography and computation
2012-11-09
Increasingly, bacteria such as E. coli are resisting the action of carbapenems by producing enzymes (carbapenemases) that break a specific chemical bond in the antibiotic, destroying its antimicrobial activity.
Carbapenemases are members of the group of enzymes called beta-lactamases that break down penicillins and related antibiotics, but it has not been clear why carbapenemases can destroy carbapenems while other beta-lactamases cannot.
Using molecular dynamics simulations, Professor Adrian Mulholland in the School of Chemistry and Dr Jim Spencer in the School of ...
ADHD medicine affects the brain's reward system
2012-11-09
A group of scientists from the University of Copenhagen has created a model that shows how some types of ADHD medicine influence the brain's reward system. The model makes it possible to understand the effect of the medicine and perhaps in the longer term to improve the development of medicine and dose determination. The new research results have been published in the Journal of Neurophysiology.
In Denmark approximately 2-3 per cent of school-age children satisfy diagnostic criteria for ADHD, and therefore it is crucial to know how the medicine works. With a new mathematical ...
New mechanism of action for PARP inhibitors discovered
2012-11-09
PHILADELPHIA — New understanding of how drugs called PARP inhibitors, which have already shown promise for the treatment of women with familial breast and ovarian cancers linked to BRCA mutations, exert their anticancer effects has led to the identification of ways in which the patient population that might benefit from PARP inhibitors could be expanded.
Yves Pommier, M.D., Ph.D., chief of the Laboratory of Molecular Pharmacology at the National Cancer Institute's Center for Cancer Research in Bethesda, Md., and colleagues reported these data in Cancer Research, a journal ...
Link found between child prodigies and autism
2012-11-09
COLUMBUS, Ohio - A new study of eight child prodigies suggests a possible link between these children's special skills and autism.
Of the eight prodigies studied, three had a diagnosis of autism spectrum disorders. As a group, the prodigies also tended to have slightly elevated scores on a test of autistic traits, when compared to a control group.
In addition, half of the prodigies had a family member or a first- or second-degree relative with an autism diagnosis.
The fact that half of the families and three of the prodigies themselves were affected by autism is surprising ...
Study questions the relevance of SCIP benchmarks among CABG patients
2012-11-09
(Boston) – Cardiothoracic surgeons and endocrinologists from Boston Medical Center (BMC) have found that among patients undergoing coronary artery bypass graft (CABG) surgery, achieving Surgical Care Improvement Project (SCIP) benchmarks for glycemic control may be irrelevant when perioperative continuous insulin infusion protocols are implemented. These findings appear on-line in the Journal of Thoracic and Cardiovascular Surgery.
Currently, 40 percent of all patients undergoing CABG suffer from diabetes, and this number is quickly rising. Traditionally these patients ...
LAST 30 PRESS RELEASES:
World’s leading science competition identifies 19 breakthrough solutions around the globe with greatest potential to tackle the planetary crisis
Should farm fields be used for crops or solar? MSU research suggests both
Study: Using pilocarpine drops post goniotomy may reduce long-term glaucoma medication needs
Stanford Medicine researchers develop RNA blood test to detect cancers, other clues
Novel treatment approach for language disorder shows promise
Trash talk: As plastic use soars, researchers examine biodegradable solutions
Using ChatGPT, students might pass a course, but with a cost
Psilocibin, or “magic mushroom,” use increased among all age groups since decriminalization in 2019
More Americans are using psilocybin—especially those with mental health conditions, study shows
Meta-analysis finds Transcendental Meditation reduces post-traumatic stress disorder (PTSD) symptoms across populations and cultures
AACR: Five MD Anderson researchers honored with 2025 Scientific Achievement Awards
How not to form a state: Research reveals how imbalanced social-ecological acceleration led to collapse in early medieval Europe
Introduced trees are becoming more common in the eastern United States, while native diversity declines
The chemical basis for life can form in interstellar ice
How safe is the air to breathe? 50 million people in the US do not know
DDT residues persist in trout in some Canadian lakes 70 years after insecticide treatment, often at levels ten times that recommended as safe for the wildlife which consumes the fish
Building ‘cellular bridges’ for spinal cord repair after injury
Pediatric Academic Societies awards 33 Trainee Travel Grants for the PAS 2025 Meeting
Advancing understanding of lucid dreaming in humans
Two brain proteins are key to preventing seizures, research in flies suggests
From research to real-world, Princeton startup tackles soaring demand for lithium and other critical minerals
Can inpatient psychiatric care help teens amid a depressive crisis?
In kids, EEG monitoring of consciousness safely reduces anesthetic use
Wild chimps filmed sharing ‘boozy’ fruit
Anxiety and depression in youth increasing prior, during and after pandemic
Trends in mental and physical health among youths
Burnout trends among US health care workers
Transcranial pulsed current stimulation and social functioning in children with autism
Hospitalized patients who receive alcohol use disorder treatment can substantially reduce heavy drinking
MSU to create first-of-its-kind database for analyzing human remains
[Press-News.org] Hunting neuron killers in Alzheimer's and TBISanford-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