Cell Death

Dateline: 06/17/99

Apoptosis, or programmed cell death, is a naturally occurring process. In recent years, it has received a lot of press as a possible key to new therapies for a host of ailments--from cancer to Parkinson's disease. Researchers at Thomas Jefferson University have recently discovered key elements of the detailed apoptosis pathway.

Researchers focused their efforts on caspase-9, an enzyme that is crucial to apoptosis. Caspases, in general, are a group of 14 cysteine proteases. These enzymes degrade essential cellular proteins. Approximately half of caspases are known to be involved in apoptosis.

From previous research, it is known that caspase-9 binds to apoptotic protease activating factor-1, a protein that helps to regulate apoptosis. But how the two bind and interact has been a mystery. Using X-ray crystallography, scientists delved into both the amino acids involved and the interactions between the two.

What they found was astounding. A key change in a critical amino acid could affect the binding between the two. A drug could exploit such a key change. If a drug inhibits the binding of the two, the pathway could be halted.

Such a disruption could halt the devastating effects of diseases such as Alzheimer's.

There are currently no caspase-based drugs on the market. Scientists hope to further their study by attempting to develop such a drug. They speculate that developing peptides that mimic the binding sequence of caspase-9 and apoptotic protease activating factor-1 may prove fruitful.

Scientists hope that by finding effective inhibitors for the action of caspase, cell apoptosis can be controlled, particularly in diseases such as cancer where cells lose the ability to die at a preset time.

What do you think? Will this research result in new therapies? What other applications might an understanding of cell death have? Come over to the Biology Forum and share your thoughts, opinions, and feelings.

For additional information see:

• Jefferson Scientists Detail Mechanisms of Programmed Cell Death
  News report about the study.