Failure of cells to die, or cells dying when they shouldn’t, can lead to or exacerbate many diseases.
Our research into how and why cells die is leading to new approaches to treating these conditions.
Our cell death researchers are:
Cell death is an important process in the body. It removes cells in situations including:
Cells can die because they are damaged, but most cells die by killing themselves.
There are several distinct ways in which a cell can die. Some occur by an organised, ‘programmed’ process. Some cell death processes leave no trace of the dead cell, whereas others activate the immune system with substances from the dead cell.
Apoptosis: is a form of cell death that prevents immune activation. Apoptotic cells have a particular microscopic appearance. The cell activates proteins called caspases that are normally dormant. These caspases dismantle the cell from within. The apoptotic cell breaks into small packages that can be engulfed by other cells. This prevents the cell contents leaking out of the dying cell and allows the components to be recycled.
Necrosis: occurs when a cell dies due to lack of a blood supply, or due to a toxin. The cells’ contents can leak out and damage neighbouring cells, and may also trigger inflammation.
Necroptosis: is similar in appearance to necrosis, in that the dying cell’s contents can leak out. However, like apoptosis, necroptosis is a programmed suicide process triggered by specific proteins in the dying cell.
Pyroptosis: is a form of cell death that occurs in some cells infected with certain viruses or bacteria. A cell dying by pyroptosis releases molecules, called cytokines, that alert neighbouring cells to the infection. This triggers inflammation, a protective response that restricts the spread of the viruses and bacteria.
Many proteins have been discovered that control whether a cell dies by the processes of apoptosis, necroptosis or pyroptosis.
Some key cell death control proteins include:
Many diseases are associated with abnormal cell death. Some examples of this are:
Understanding how proteins such as the Bcl-2 family control cell death has led to the development of new drugs to block their function. These have the potential to cause the death of cancer cells, or the immune cells that cause autoimmune disease.
One set of drugs, called ‘BH3 mimetics’ trigger apoptotic cell death. They do so by preventing the action of ‘pro-survival’ Bcl-2 family proteins. Unless blocked, these pro-survival proteins help cancer cells stay alive, even after anti-cancer treatments such as chemotherapy.
Clinical trials are underway to determine whether BH3 mimetics can be used to treat certain cancers. BH3-mimetics might also potentially help treat autoimmune diseases by killing disease-causing white blood cells.
SMAC-mimetics are agents that, like the SMAC protein, enhance cell death. They do this by stopping IAPs from blocking cell death. They might also be able to help cells die so that chronic viral infections can be cleared.
There is also considerable interest in agents that can prevent cell death. These could have applications for treating conditions in which there is unwanted cell death, such as stroke, heart attack or neurodegenerative disorders.