A new study published in the June 2002 issue of Developmental Cell unveiled a new discovery in the process of cell death in Huntington disease (HD), and another potential strategy for the development of a treatment.

Researchers from the Curie Institute in France, as well as the Harvard Medical School and the Gladstone Institute for Neurological Disorders at the University of California, have identified important chemical interactions at the cellular level that are able to inhibit the process of programmed cell death (apoptosis) that is created by mutant huntingtin.

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Apoptosis is the self-destruct sequence for a cell. Previous articles of Horizon have provided details on the importance of caspase inhibition as a way of slowing down the process of apoptosis in a brain affected by HD. When a cell becomes too old, or is unable to function properly, it initiates apoptosis so that it can be destroyed. Caspases are molecules that play an important part in this self-destruct sequence, but they are not the only player in the process.

This new study demonstrates that it is possible to slow apoptosis by interacting with something called the Akt pathway, another important player in the process of apoptosis. The Akt pathway functions as a transmitter, sending signals that call into action other players in the process of apoptosis, such as caspases. Researchers showed that by introducing a chemical called insulin growth factor 1 (or IGF-1), it is possible to "turn on" the Akt pathway, which then modifies mutant huntingtin and stalls the ability of the cell to self-destruct through apoptosis.

In addition to its ability to block the process of apoptosis, the introduction of IGF-1 also led to a reduction in the formation of protein aggregates (or protein balls) formed by mutant huntingtin in the cell. It is these protein aggregates made up of the mutant or toxic huntingtin that ultimately cause brain cells to trigger the process of apoptosis - the cell's self-destruct system - in the first place.

According to the research team, further study of the nature of the IGF-1/Akt pathway and its ability to stall apoptosis, and consequently protect brain cells, would be valuable -possibly identifying new options for treating HD. - SM

Can you translate that for me?

Apoptosis is a process that cells use to self-destruct if they are damaged or can no
longer work properly. In the brain of a person with HD, mutant huntingtin
(produced by the mutant gene that causes HD) creates toxic lumps of the mutant
huntingtin protein in the brain cells, and causes the cells to start the process of
apoptosis - the cell's self-destruct sequence.

In this study, researchers observed that a chemical called insulin growth factor 1
(IGF-1) activates or "turns on" a key player in apoptosis called the Akt protein.
The Akt protein works like a transmitter, sending signals to key parts of the cell to
inhibit or "stall" apoptosis. When IGF-1 turns on Akt, mutant huntingtin is one of
several proteins that is modified or altered by Akt. This alteration of the mutant
huntingtin helps to delay the self-destruct sequence (apoptosis) and extend the life
of the cell.

The researchers in this study see this result as another possible approach for the
development of a treatment for HD.