BH3-mimetics might be new option for treatment of autoimmune conditions

Published on January 23, 2013 at 10:29 PM · No Comments

Melbourne researchers have discovered that the death of immune system cells is an important safeguard against the development of diseases such as type 1 diabetes, rheumatoid arthritis and lupus, which occur when the immune system attacks the body's own tissues.

The finding suggests that these so-called autoimmune diseases could be treated with existing medications that force long-lived immune system cells to die.

In the development of the immune system, some cells are produced that have the potential to attack the body's own tissues, causing autoimmune disease. The death of these 'self-reactive' immune cells through a process called apoptosis is an important safeguard against autoimmune disease.

But Dr Kylie Mason, Dr Lorraine O'Reilly, Dr Daniel Gray, Professor Andreas Strasser and Professor David Huang from the Walter and Eliza Hall Institute, and Professor Paul Waring from the University of Melbourne have discovered that when immune cells lack two related proteins, called Bax and Bak, the cells can attack many healthy tissues, causing severe autoimmune disease. The research is published online today in the journal Proceedings of the National Academy of Sciences.

Bax and Bak are members of the 'Bcl-2 protein family', a large group of proteins that control cell death. Dr O'Reilly said it was thought that Bax and Bak acted like an irreversible switch in cells, determining when cells die by apoptosis. In healthy cells, Bax and Bak are in an 'inactive' form, but when cells are under stress or receive external signals instructing them to die, Bax and Bak switch into an 'active' form that starts the destruction of the cell by apoptosis. Without Bax and Bak, cells are highly protected against apoptosis.

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