Targeting MAPK Phosphorylation of Connexin43 Provides Neuroprotection in Stroke
This week we profile a recent publication in the Journal of Experimental Medicine
from the laboratory of Dr. Christian Naus (pictured) at UBC.
Can you provide a brief overview of your lab’s current research focus?
The objective of my lab’s research program is to explore the role of gap junction channels and hemichannels in neural development and disease, including consequences of connexin mutations on gap junction channel structure and function, and to explore the role of these intercellular channels in diagnosis of disease and development of novel therapeutic strategies.
What is the significance of the findings in this publication?
In this study, we successfully used a new approach that significantly minimized brain damage caused by stroke in mouse models. The new approach works by targeting hemichannels—pathways that allow for the flow of chemical ions and small molecules—that are expressed by astrocytes, cells that play a protective role for neurons in the brain.
When stroke occurs, these hemichannels open and can leak toxic molecules into the space outside the astrocytes, causing inflammation and damage to neurons. Our study definitively confirms that hemichannels are detrimental in stroke, and that we can block them to minimize damage to the brain. A lot of previous research has focused on trying to protect neurons, but here we sought a way to enhance the astrocyte’s ability to protect neurons in stroke. This research is a great example of how the expertise from laboratories from three different countries could not only identify the importance of these connexin hemichannels but also discover the mechanisms involved and even identify possible avenues for treatment.
What are the next steps for this research?
It was important for us that we used a clinically realistic treatment window, two hours after the stroke event, especially if we were testing a drug that could potentially be used for treatment one day. Clearly this is the next step in this research, to explore opportunities for a clinical trial.
This work was funded by:
This research was supported by grants from the Heart and Stroke Foundation of Canada, the Canadian Institutes of Health Research, the Canada Research Chairs program, the U.S. National Institutes of Health, the Fund for Scientific Research Flanders, the Interuniversity Attraction Poles Program, and the Geneeskundige Stichting Koningin Elisabeth.