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2016 Grants - Rangaraju
Ion Channels: Regulators of Neuroinflammation in Alzheimer’s Disease
Srikant Rangaraju, M.B.B.S.
2016 Alzheimer’s Association Research Grant (AARG)
How do immune cells in the brain have both pro-inflammatory and anti-inflammatory effects during Alzheimer’s disease?
During Alzheimer’s disease there is inflammation in the brain (neuroinflammation) resulting from activation of the brain’s immune system. While this process can be protective, excess inflammation can be damaging to nerve cells. The brain contains specialized cells known as microglia, which function as part of the immune system. Like other parts of the immune system, the activity of microglia is controlled by complex networks of cells and molecules. Such control is essential, since microglia can cause damage to healthy nerve cells when they are overactive. One way in which the function of microglia is regulated is through ion channels which allow electrically charged ion molecules to flow in and out of the cell. Novel treatments aimed at manipulating these channels may help to regulate microglia in the brain during Alzheimer’s disease.
Srikant Rangaraju, M.B.B.S. and colleagues will determine how three specific types of microglia ion channels may regulate neuroinflammation. In initial experiments using microglia growing in laboratory dishes, the researchers identified one type of channel associated with “proinflammatory” factors and two channels associated with “anti-inflammatory factors” — suggesting that microglia can have both beneficial and harmful effects on the brain. For their current studies, the researchers will systematically block each channel in the brains of Alzheimer’s-like mice and measure the effect on levels of inflammatory molecules and nerve cell damage. They hypothesize that blocking the pro-inflammatory channel may reduce neuroinflammation in Alzheimer’s-like mice, potentially slowing disease progression.
The results of this work could shed new light on how neuroinflammation occurs during Alzheimer’s disease. The study may also reveal a novel way to regulate the function of microglia as a therapeutic approach to slow or prevent Alzheimer’s disease.