Spring 1995 Volume 4, Number 2
Before birth, a normal, gene-controlled event called "programmed cell death" helps shape the brain. The process involves fragmentation of DNA in the doomed cells which then are engulfed by neighboring cells. The genes for the death program switch off once the brain is formed. However, DNA fragmentation resembling programmed cell death has been noted in stroke and certain brain diseases, suggesting that disease or injury pathology may re-activate cell death genes in the mature brain -- and make lethal a possibly survivable situation.
Junying Yuan and her colleagues at Massachusetts General Hospital are preparing to test this hypothesis for amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig's disease, a fatal disease in which motor neurons degenerate and die, and in a mouse model of stroke. Yuan's team is working with a family of genes, called "Ice" genes, that they identified in 1993. The researchers found that Ice genes are essential to programmed cell death and in cultured tissue experiments that a molecule called CRMA inhibits the action of Ice genes in neurons, allowing the nerve cells to survive under conditions in which they would normally die.
Now Yuan's group is cross-breeding a batch of mice genetically bred to develop ALS, with mice carrying a suppressor of Ice family genes. The investigators will test the cross-bred offspring to see if the inhibitor can stop or reduce the death of motor neurons. If it works, the team will have identified a promising drug strategy for intervention in the course of this disease.
