Pleiotropy
The products of many genes have several different effects or phenotypes in cells, a phenomenon known as pleiotropism or pleiotropy. Levels of pleiotropy vary from one gene to another, giving rise to expressions such as low-pleiotropy or great pleiotropy in the published scientific literature.
Genes encoding cytokines, polypeptide hormones used in cell-to-cell communication, may have many pleiotropic effects and, therefore, present great pleiotropy, as well as great redundancy because many functions of a given cytokine may also be performed by other different cytokines. For instance, several different cytokines may induce activated lymphocytes T (T cells) into proliferation. Examples of cytokines are as follows: Interferon alpha and beta (IFNalfa and IFNbeta), tumor necrosis factor (TNFalfa), interleukin-1 (IL-1alfa and IL-1beta).
Another example of great pleiotropy is given by GAPDH (enzyme glyceraldehyde-3-phosphate dehydrogenase). GAPDH was first known by its role in the metabolism of glucose, but several research groups gradually found that it played several different roles in different tissues, such as regulation of protein translation, export of RNAt from cell nucleus to cytoplasm, a role in DNA repair, a role in DNA replication, and another role in cell membrane during phagocytosis.
Some authors also use the term pleiotropism or pleiotropy when referring to synthetic molecules that present different effects in different disorders. For example, aspirin (acetyl salicylic acid) that has well-known analgesic (pain killing) and antipyretic (anti fever) effects, but also helps to reduce atheroma formation (plaques that sediment in veins and arteries, causing circulatory disorders), and more recently, has shown some anti tumor properties. Another example of a pleiotropic medicine is COX-2 (cyclooxygenase-2) inhibitors, first developed as an anti-inflammatory drug, and now under scrutiny by cancer researchers because of its anti tumor effects as an adjuvant treatment of cancer as well as a chemo preventive therapy. COX-2 is a member of a family of enzymes, the COX enzymes, and it is found overexpressed in colorectal tumors and other cancers. Cox genes are housekeeping genes that also present a great pleiotropism.
Thalidomide, first developed for treatment of nausea during pregnancy, caused thousands of cases of birth defects because it was unknown at that time that it is also an inhibitor of blood vessels' formation (angiogenesis). Presently, it is being prescribed as an antiangiogenic drug for cancer patients because it prevents tumor neovascularization (new vein formation), thus helping to control tumor growth. Several studies also indicate that some antibiotics of the molecular group of macrolides, such as chlarithromycin, do present a powerful antiangiogenic effect over some lung tumors.
The pleiotropic effect of several drugs, such as those mentioned above, may present an interesting field for biomedics, and a potential advantage to patients, because they are already marketed and tested as far as toxicity is concerned. However, they may end up as orphan drugs for other disorders, because they may never be adequately tested and standardized for new diseases, since it would require new investments in clinical trials.
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