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What is a CASPASE?

Caspases made headline news in the Huntington's world when Dr. Robert Friedlander and his colleagues in Boston announced that they could delay the onset of symptoms in a mouse model of Huntington's disease by blocking something called caspase-1. So what are caspases, and could they really be the "magic bullet" against neurodegenerative diseases, as one researcher predicted?

Caspases are enzymes involved in the destruction of cells. In a normal, healthy human being, damaged or mutated cells are regularly destroyed to protect the rest of the body. For example, if a cell turns cancerous, caspases destroy the cell before the cancer can spread. This normal process of programmed cell death is called "apoptosis".

However, in a person with Huntington's disease, apoptosis goes out of control, and large areas of brain tissue are destroyed. Dr. Friedlander found that by blocking the action of one of these caspases, he could slow down the destruction of brain cells.

There are several caspases involved in apoptosis. "Initiator" caspases are responsible for kick-starting the process of cell death in response to some external signal, and for activating the "effector" caspases. Effector caspases actually execute the process - they are responsible for breaking down the cell.

In Huntington's disease, it seems that the abnormal huntingtin protein triggers this sequence. An initiator caspase responds to the presence of the huntingtin protein by cutting it into smaller pieces. These smaller pieces of huntingtin activate effector caspases, which in turn cut up more huntingtin, and create a whole cascade of caspase activity, ending in the death of the cell.

Dr. Friedlander succeeded in delaying the onset of symptoms and extending the total lifespan of Huntington's disease mice by blocking caspase-1, preventing the huntingtin protein from being cut up. In other research, scientists have shown that blocking caspase-8 can prevent cell death, and blocking other caspases could well have similar effects.

It is important to note that caspases may not be the only enzymes involved in cell death, so even if all the caspases are blocked, cell death may still occur. There is no doubt, however, that caspase research is showing a great deal of promise.