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!
Aquaculture: Clear Water Thanks to Cork
28.10.2016 | Technologie Lizenz-Büro (TLB) der Baden-Württembergischen Hochschulen GmbH
Bioluminescent sensor causes brain cells to glow in the dark
28.10.2016 | Vanderbilt University
Physicists from the University of Würzburg have designed a light source that emits photon pairs. Two-photon sources are particularly well suited for tap-proof data encryption. The experiment's key ingredients: a semiconductor crystal and some sticky tape.
So-called monolayers are at the heart of the research activities. These "super materials" (as the prestigious science magazine "Nature" puts it) have been...
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
28.10.2016 | Power and Electrical Engineering
28.10.2016 | Life Sciences
28.10.2016 | Life Sciences