Role of Apoptosis in Health and Disease
Apoptosis occurs during the normal development of multicellular organisms and continues throughout adult life. The combination of apoptosis and cell proliferation is responsible for shaping tissues and organs in developing embryos. For example the apoptosis of cells located in-between the toes allows for their separation.
Apoptosis is also an important part of the regulation of the immune system. T lymphocytes are cells of the immune system that are responsible for destroying infected or damaged cells in the body. They mature in the thymus, but before they can enter the bloodstream they are tested to ensure that they are effective against foreign antigens and are also not reactive against normal, healthy cells. Any ineffective or self-reactive T-cells are removed through the induction of apoptosis.
Problems with the regulation of apoptosis have been implicated in a number of diseases. Cancer is a disease that is often characterized by too little apoptosis. Cancer cells typically possess a number of mutations that have allowed them to ignore normal cellular signals regulating their growth and become more proliferative than normal. Under normal circumstances damaged cells will undergo apoptosis, but in the case of cancer cells mutations may have occurred that prevent cells from undergoing apoptosis. In these cases there is no check on the cellular proliferation and consequently the disease can progress to the formation of tumors. In many cases these tumors can be difficult to kill as many cancer treatments rely on damaging the cells with radiation or chemicals and mutations in the apoptotic pathway often produce cells that are resistant to this type of attack. Understanding how apoptosis is regulated in cancer is therefore of major interest in the development of treatments for this disease.
If cancer is a disease where too little apoptosis occurs there are other diseases where too much apoptosis is thought to be part of the problem. For example in neurodegenerative diseases such as Parkinson's or Alzheimer's Diseases apoptosis is thought to account for much of the cell death and the progressive loss of neurons.
During pregnancy trophoblast cells from the placenta invade the uterine environment in order to remodel the maternal blood vessels and help establish and maintain a successful pregnancy. Strict control over cell proliferation and apoptosis is required to achieve this. In some cases this process can be compromised and excessive apoptosis of the trophoblast cells is thought to be implicated in the failure to fully remodel the maternal environment that is observed in complications of pregnancy such as preeclampsia.
Apoptosis is also thought to play a role in the progression of many auto-immune diseases. For example, in the case of rheumatoid arthritis excessive proliferation of synovial cells is thought to be due in part to the resistance of these cells to apoptotic stimuli. In other cases poor regulation of apoptosis in T-lymphocytes can result in auto-reactive T-cells entering the circulation and contributing to the onset of autoimmune diseases.
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