Autophagy in Human Health and Disease

There are a number of biological processes which can influence the progression and pathogenesis of diseases experienced by humans. Upon identifying the number of processes which can contribute to a disease state, being inflammation, apoptosis, and metabolism, it can be concluded that these pathways are critical in treating a particular disease state. Recently, these pathways have been the targets of various drug pathways. The most notable of which is the process of autophagy.  The process of autophagy occurs in response to regulatory cues stimulated by environmental factors.  Simply, autophagy is the ability of a cell to consume debris and particles outside of a cell. Primarily, this process serves as a protective mechanism to prevent cell death.  Many processes that involve disease states are identified. The development of cancer can be both inhibited and facilitated through autophagy.  In existing tumors, autophagy can be used by the tumor cells to prolong survival, where autophagy regulates or inhibits the initiation of cancer in healthy cells. In neurodegenerative diseases, it is found that the processes involving autophagy are altered. Autophagic enzymes are often over expressed in a compensatory type fashion to existing neurodegenerative diseases, or under expressed as the neurodegenerative disease inhibits their function or formation.  Pathways for autophagy also exist within infectious disease responses. Autophagy helps in the elimination of diseases such as herpes encephalitis, bacterial infections such as salmonella, and parasites while aiding in the cleaning of debris from immunologic responses.

As the role of autophagy in the development and pathogenesis of diseases, the applications in targeting these pathways are of value.  Currently, anticancer drug Sirolimus activates autophagy as an immunosuppressive drug and anticancer drug.  A progression in our understanding of autophagy will elicit further drug targets and ways in which the pathogenesis of diseases can be inhibited.

N Engl J Med 2013; 368:651-662February 14, 2013http://www.nejm.org/doi/full/10.1056/NEJMra1205406

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