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."
Sanford-Burnham Medical Research Institute: http://www.burnham-inst.org
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
With funding from the Defense Department, scientists have begun work on devices that would use electric pulses to realign a memory process gone awry
On Friday, the Food and Drug Administration released a vital set of numbers about the routine use of antibiotics …
Side order of veg with that mammoth leg? The Neanderthal diet was probably more varied than we think – using vegetables, herbs and different cooking techniques
An exoskeleton that enables movement and provides tactile feedback has helped eight paralysed people regain sensation and move previously paralysed muscles
A female western gray whale set a new record swimming from Russia to Mexico and back, a total of 13,988 miles, in 172 days
Scientists operating a remote-controlled vehicle about 2,000 feet below water get a rare glimpse of a sperm whale. CBSN's Vladimir Duthiers and Elaine Quijano report on the video.
According to the experts, "blinking is like a kitty kiss"
Genetic profiling of cancer cells can help guide treatment, but such profiles can be ambiguous. Results would be more accurate if all labs tested normal cells from each patient, too.
Researchers in Kenya uncover tools dated to 3.3 million years ago, long before the first humans, as we know them, walked the Earth.
Researchers are facing up to methodological flaws that plague functional magnetic resonance imaging, but the interpretative problems might be harder to solve