A possible drug target for stroke patients?

As we know a transient ischemic attack (TIA), or stroke, occurs when there is an occlusion or rupture in a blood vessel in the brain, blocking or reducing blood flow from an area of the brain, resulting in damage and usually mental or physical deficits.

But also, these damaged areas undergo a lot of oxidative stress in the days following a stroke, releasing reactive oxygen species.  In the brain, this oxidative stress can reduce memory and cognitive function in stroke patients.

Now labs in the United Kingdom and in China have found a certain type of ion channel, TRPM2, in the plasma membrane of neurons, which gets activated and opened by these reactive oxygen species released following a stroke (Figure 1).  To test their findings they used a murine model, in which some mice had a properly functioning TRPM2 ion channel, and some mice had an inactivated TRPM2 ion channel.  Then, in all mice they induced oxidative stress.

 

Figure 1.

The researchers found that mice with an inactivated TRPM2 ion channel had much lower levels of neuronal cell death and performed better in memory tests than mice with the active TRPM2.

What does this mean?  This suggests that blocking this ion channel in patients who have recently had a stroke would decrease the damage from oxidative stress and be protective against the cognitive decline after a stroke.  This would make an excellent drug target!

The lab’s next plan is to test this ion channel against a chemical library and see if any compounds inactive the TRPM2 ion channel.  If they did find one it would provide an excellent option for treating patients who have experienced a stroke.

McNamee, D. (2014, November 28). "Drug target identified for prevention of stroke-related brain damage." Medical News Today. Retrieved from
http://www.medicalnewstoday.com/articles/286220.php.

TRPM2 channel deficiency prevents delayed cytosolic Zn2+ accumulation and CA1 pyramidal neuronal death after transient glo Q1 bal ischemia, Cell Death and Disease, doi:10.1038/CDDIS.2014.494, published online 27 November 2014.

Figure 1:  http://jp.physoc.org/content/589/7/1515/F3.large.jpg