The role of apoptosis in autoimmune thyroid disorders and thyroid cancer

Apoptosis, or programmed cell death, is an active process of self destruction that requires the activation of a genetic programme that may lead to changes in cell morphology, DNA fragmentation, and protein cross linking.1 Apoptosis can be triggered in several ways and involves many cellular functions.2 The mechanism provides protection from the possible consequences of uncontrolled cell proliferation, which could lead to neoplasia. Cell death is a factor in the pathogenesis of several diseases, including autoimmune disorders, cancer, AIDS, and neurodegenerative diseases. Regulation of apoptosis in cells undergoing proliferation may be the key to reversing the natural progression of these disorders.3 Apoptosis involves the sequential activation of a series of caspases, which are proteolytic enzymes that degrade a number of death substrates. Caspase is activated by two pathways—the mitochondrial pathway and the death receptor pathway—and thereby may trigger nuclear enzymes to degrade chromosomal DNA and alter mitochondrial function. Specific pathways and non-specific signals (such as cytotoxic drugs and radiation) may activate caspase. The most common of these pathways involves death receptors that have structures belonging to the tumour necrosis factor (TNF) receptor superfamily of proteins. Interaction of tumour necrosis factor with this receptor can induce cell death by the activation of various kinase enzymes that act as secondary messengers within the cell.4 Another member of this family, Fas antigen, and its ligand (FasL), are molecules used by immune effector cells to kill targets.5