Researchers at the University of North Carolina at Chapel Hill have discovered a molecule that can make brain cells resistant to programmed cell death or apoptosis.
They then decided to pinpoint where exactly this molecule played a role in the series of biochemical events leading to cell death. The researchers looked at a number of steps in apoptosis and found that miR-29 acts at a key point in the initiation of apoptosis by interacting with a group of genes called the BH3-only family. Interestingly, the microRNA appears to interact with not just one but as many as five members of that family, circumventing a redundancy that existed to allow cell death to continue even if one of them had been blocked.
"People in the field have been perplexed that when they have knocked-out any one of these members it hasn’t had a remarkable effect on apoptosis because there are others that can step in and do the job," said Deshmukh. "The fact that this microRNA can target multiple members of this family is very interesting because it shows how a single molecule can basically in one stroke keep apoptosis from happening. Interestingly, it only targets the members that are important for neuronal apoptosis, so it may be a way of specifically preserving cells in the brain without allowing them to grow out of control (and cause cancer) elsewhere in the body."
Deshmukh is currently developing mouse models where miR-29 is either "knocked-out" or overactive and plans to cross them with models of Alzheimer’s disease, Parkinson’s disease and ALS to see if it can prevent neurodegeneration. He is also actively screening for small molecule compounds that can elevate this microRNA and promote neuronal survival.
SOURCE University of North Carolina at Chapel Hill