They report their findings in the Journal of Biological Chemistry article, "Fibrillar Beta-Amyloid Stimulated Intracellular Signaling Cascades Require Vav for Induction of Respiratory Burst and Phagocytosis in Monocytes and Microglia."
The researchers discuss the role that the multi-domain protein Vav plays in the intercellular signaling of microglia, the brain's primary immune cell, when it produces an inflammatory response when coming into contact with beta-amyloid fibrils that form the harmful brain plaque.
The primary goal of this study was to evaluate potential signaling intermediates upstream from the oxidation, said the researchers. They had an interest in a group of signaling molecules (guanine nucleotides exchange factors) that are known to activate oxidation. Vav was selected from the group for study.
The inflammatory response that arise when the microglia connects with the plaque has been suspected as producing the oxidative damage observed in both human and animal models of AD, report the researchers.
This current study builds on prior research studies that produced evidence of the microglia mounting this inflammatory immune response by whittling down the various components in that reaction.
"We have recently shown that microglia employ a multi-receptor cell surface complex to detect and respond to amyloid –beta fibrils," the researchers write. "These receptor elements act in concert to stimulate intercellular signaling cascades as well as initiate a novel type of phagocytosis (cell death) in microglia."
"Vav has been found to be the key regulatory element within the intercellular signaling cascade," said Brandy Wilkinson, the study's lead researcher. Her co-investigators are Jessica Koenigsknecht-Talboo, Christian Grommes, C.Y. Daniel Lee and Gary Landreth from the Alzheimer Research Laboratory in the Case department of neuroscience. Vav also plays a critical role in the initial microglial response to the plaque.
Oxidative damage has long been suspected as playing an early critical role in AD. Because the events that trigger the beginnings of AD are still unknown, the Case researchers began targeting research on the reaction between the plaque and immune cells.
In in vitro studies of brain tissue from mice, the researchers found that the microglia had the appropriate immune response that the plaque was harmful, but then the protein Vav was found to be a component in oxidative damage since elimination of the protein resulted in reduced free radical production.
Wilkinson said by understanding this biological component in the disease process, it holds the potential to "push back the severity of the disease" by developing new drugs that specifically target the component causing the most destruction and decreasing the possibility of injuring or interrupting other biological processes.
Susan Griffith | EurekAlert!
The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences
Transforming plant cells from generalists to specialists
07.12.2016 | Duke University
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
07.12.2016 | Health and Medicine
07.12.2016 | Life Sciences
07.12.2016 | Health and Medicine