Department of Neuroscience faculty, Candice Askwith, PhD has embarked on a five year project with the help of grant funding from the NIH to investigate novel mechanisms to prevent neuron death following ischemic stroke.
A variety of pathological mechanisms contribute to neuronal death and permanent brain injury following cerebral ischemia and ischemic stroke. Yet, there are sparingly few therapeutics that have been shown to protect neurons in clinical trials of stroke. One avenue that has remained unexplored is targeting the acid sensing ion channels (ASICs). During cerebral ischemia, the pH in the brain becomes acidic for hours, even after blood flow returns to normal. Under these conditions, ASICs initiate neuronal death and targeting these ion channels, even when compounds are administered hours after an ischemic event, has shown therapeutic benefit in animal models. However, there are no approved drugs that directly target ASICs in humans. Further, ASICs play an important role in the brain, particularly for learning and memory.
In this grant, Dr. Askwith and her research team will examine how ASIC-dependent toxicity in neurons can be limited by cellular signaling cascades initiated by activation of specific G protein-coupled receptors. An exciting aspect of this work is that this strategy uses existing drugs to target acid-dependent toxicity in neurons and does not appear to impact ASIC function under normal conditions. The knowledge created from this work will lay the foundation for the development of novel strategies to target ASIC channels and prevent neuronal damage after stroke and ischemia.