A new target for the prevention of adverse immune responses identified as factors in the development of Alzheimer's disease (AD) has been discovered by researchers at the University of South Florida's Department of Psychiatry and the Center of Excellence for Aging and Brain Repair.
Their findings are published online in the Journal of Neuroscience (http://www.jneurosci.org/).
The CD45 molecule is a receptor on the surface of the brain's microglia cells, cells that support the brain's neurons and also participate in brain immune responses.
Previous studies by the USF researchers showed that triggering CD45 was beneficial because it blocked a very early step in the development of Alzheimer's disease. In the present study, the researchers demonstrated in Alzheimer's mouse models that a loss of CD45 led to dramatically increased microglial inflammation.
Although the brain's immune response is involved in Alzheimer's disease pathology, "this finding suggests that CD45 on brain immune cells appears critically involved in dampening harmful inflammation," said study senior author Jun Tan, MD, PhD, a professor of psychiatry and Robert A. Silver chair at the Rashid Laboratory for Developmental Neurobiology, USF Silver Child Development Center and research biologist for Research and Development Service at the James A. Haley Veteran's Hospital.
The investigators also found an increase in harmful neurotoxins, such as A beta peptides, as well as neuron loss in the brains of the test mice.
"In short, CD45 deficiency leads to increased accumulation of neurotoxic A beta in the brains of old Alzheimer's mice, demonstrating the involvement of CD45 in clearing those toxins and protecting neurons," Dr. Tan said. "These findings are quite significant, because many in the field have long considered CD45 to be an indicator of harmful inflammation. So, researchers assumed that CD45 was part of the problem, not a potential protective factor."
The next step is to apply these findings to develop new Alzheimer's disease treatments, said Paula Bickford, PhD, a professor in the USF Department of Neurosurgery and senior career research scientist at the James A. Haley Veteran's Hospital.
"We are already working with Natura Therapeutics, Inc. to screen for natural compounds that will target CD45 activation in the brain's immune cells," Dr. Bickford said.
Other researchers involved in this study were: Dr. Yuyan Zhu, Dr. Huayan Hou, Dr. Kavon Rezai-zadeh, Dr. Brian Giunta, Ms. Amanda Ruscin, Dr. Carmelina Gemma, Dr. JingJi Jin, Dr. Natasa Dragicevic, Dr. Patrick Bradshaw, Dr. Suhail Rasool, Dr. Charles G. Glabe (University of California, Irvine, CA), Dr. Jared Ehrhart, Dr. Takashi Mori (Saitama Medical Center/Saitama Medical University, Japan), Dr. Demian Obregon, Dr. Terrence Town (Cedars-Sinai Medical Center, Los Angeles, CA). Drs. Yuyan Zhu and Huayan Hou contributed equally to this work.
Their work was supported by the National Institute on Aging and the National Institute of Neurological Disorders and Stroke, National Institutes of Health.
The mission of the Center of Excellence for Aging and Brain Repair is to develop new therapeutic strategies to promote repair and regeneration of aging and diseased brain. Building on a foundation of excellence in basic and clinical research, we focus on translating innovative ideas into industrial partnerships, educational and clinical services to address key needs of the community and those suffering from brain injury and disease.
USF Health (www.health.usf.edu) is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida's colleges of medicine, nursing, pharmacy and public health; the schools of biomedical sciences as well physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $394.1 million in research grants and contracts in FY2009/2010, the University of South Florida is one of the nation's top 63 public research universities and one of only 25 public research universities nationwide with very high research activity that is designated as community-engaged by the Carnegie Foundation for the Advancement of Teaching.
Randolph Fillmore | EurekAlert!
Routing gene therapy directly into the brain
07.12.2017 | Boston Children's Hospital
New Hope for Cancer Therapies: Targeted Monitoring may help Improve Tumor Treatment
01.12.2017 | Berliner Institut für Gesundheitsforschung / Berlin Institute of Health (BIH)
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications
Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...
Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.
The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
11.12.2017 | Physics and Astronomy
11.12.2017 | Earth Sciences
11.12.2017 | Information Technology