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Case Western Reserve University researchers find protein associated with brain cell death

Neuroscientists at the Case Western Reserve University School of Medicine have found evidence of which protein in the brain's immune cells triggers a cascade of reactions that produces unregulated free radical production that eventually leads to the neural cell death found in Alzheimer's disease.

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
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Source:Case Western Reserve University


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