An animal study supported by the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, shows that by targeting the blood-brain barrier, researchers are able to slow the accumulation of a protein associated with the progression of the illness.
The blood-brain barrier separates the brain from circulating blood, and it protects the brain by removing toxic metabolites and proteins formed in the brain and preventing entry of toxic chemicals from the blood.
“This study may provide the experimental basis for new strategies that can be used to treat Alzheimer’s patients,” said David S. Miller, Ph.D., chief of the Laboratory of Toxicology and Pharmacology at NIEHS and an author on the paper that appears in the May issue of Molecular Pharmacology.
Alzheimer’s is an irreversible, progressive brain disease that slowly destroys memory and thinking skills, and eventually disrupts function of major organs. Estimates vary, but experts suggest that as many as 2.6 million to 5.1 million Americans may have Alzheimer’s. One hallmark of Alzheimer’s is the deposition of beta-amyloid protein in the brain. This protein clumps to form plaques that destroy neurons and lead to cognitive impairment and memory loss in Alzheimer patients.
“What we’ve shown in our mouse models is that we can reduce the accumulation of beta-amyloid protein in the brain by targeting a certain receptor in the brain known as the pregnane X receptor, or PXR,” said Miller.
The researchers from NIEHS and the University of Minnesota Duluth demonstrated that when 12-week-old genetically modified mice expressing human beta-amyloid protein are treated with a steroid-like chemical that activates PXR, the amount of beta-amyloid protein in the brain is reduced. The activation of the PXR was found to increase the expression of a blood-brain barrier protein known as P-glycoprotein. This protein transports beta-amyloid out of the brain.
“Our results show several new findings. We now know that P-glycoprotein plays a pivotal role in clearing beta-amyloid from the brain. Secondly, we know P-glycoprotein levels are reduced in the blood-brain barrier, and that the Alzheimer’s mice treated with the chemical to activate PXR were able to reduce their beta-amyloid levels to that of mice without Alzheimer’s,” said Bjorn Bauer, Ph.D., assistant professor at the University of Minnesota and senior author on the paper.
Anika Hartz, Ph.D., lead author on the study, added that it is also likely that reduced P-glycoprotein expression at the blood-brain barrier may be an early indicator of Alzheimer’s disease, even before the cognitive symptoms appear. One of the challenges confronting the diagnosis and treatment of Alzheimer’s is being able to clearly diagnose the disease process when brain damage is minimal, before any symptoms occur.
“More research is needed before this animal model discovery can be tested in humans, but the paper suggests some new targets for treatment that offer hope to patients and families dealing with this devastating disease,” said NIEHS Director Linda Birnbaum, Ph.D.
The researchers plan to conduct a study where the Alzheimer’s mice are fed a PXR-activating compound in their diet for 12-18 months. The cognitive skills of the animals will be monitored regularly, along with their P-glycoprotein levels, to determine whether the feeding regimen delays the onset of cognitive impairment.
The NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit our Web site at http://www.niehs.nih.gov. Subscribe to one or more of the NIEHS news lists (http://www.niehs.nih.gov/news/releases/newslist/index.cfm) to stay current on NIEHS news, press releases, grant opportunities, training, events, and publications.
The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
Reference(s): Hartz AM, Miller DS, Bauer, B. 2010. Restoring Blood-Brain Barrier P-glycoprotein Reduces Brain Abeta in a Mouse Model of Alzheimer’s Disease. Mol Pharmacol. Online January 25, 2010.doi:10.1124/mol.109.061754.
Robin Mackar | Newswise Science News
'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS
New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).
Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
16.02.2018 | Information Technology
16.02.2018 | Health and Medicine
16.02.2018 | Physics and Astronomy