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Vol. 97 No. 4 April 2004


Editor: Alan R. Gould

The role of apoptosis in oral disease: Mechanisms; aberrations in neoplastic, autoimmune, infectious, hematologic, and developmental diseases; and therapeutic opportunities
Nikolaos G. Nikitakis, DDS, PhD,a John J. Sauk, DDS, MS,b and Stavros I. Papanicolaou, DDS, MD, MSc, DrDent,c Baltimore, Md, and Athens,Greece

Apoptosis is a genetically programmed form of cell death, which primarily functions to eliminate senescent or altered cells that are useless or harmful for the multicellular organism. Contrary to necrosis, apoptosis represents a physiologic cellular mechanism, normal function and control of which are critical for the development andhomeostasis of multicellular organisms. In contrast, aberrations of the apoptotic mechanisms that cause excessive or deficient programmed cell death have been linked to a wide array of pathologic conditions. This review briefly summarizes the major apoptotic pathways and molecules and presents the most important oral diseases that are related to dysregulation of apoptosis. Knowledge of the associationbetween aberrations in apoptotic mechanisms and human pathology hopefully will be implemented for the design of improved diagnostic and prognostic assays and the development of novel, more efficient, therapeutic strategies. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;97:476-90)

In multicellular organisms, the number of cells is determined by a tightly regulated equilibrium between cellproliferation and cell death. Maintenance of this balance is a prerequisite for unhampered development and growth as well as for homeostasis of adult tissues. Although these principles date back to ancient Greek and Roman physicians and were broadly accepted since the 19th century,1 the existence and importance of a physiologic cell death program remained unrecognized until 1972, when Kerr and hisassociates introduced the term apoptosis, derived from the Greek word for ‘‘dropping off’’ or ‘‘falling off’’ of petals from flowers or leaves from trees.2 In contrast to necrosis (the form of cell death that results from excessive cell injury due to an external pathologic stimulus), apoptosis represents a physiologic


Assistant Professor, Department of Diagnostic Sciences and Pathology,University of Maryland, Baltimore. . b Professor and Chair, Department of Diagnostic Sciences and Pathology, University of Maryland. . c Professor and Chair, Department of Oral Pathology, Faculty of Dentistry, University of Athens, Greece. . 1079-2104/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.tripleo.2003.12.032

cellular mechanism of programmed cell death, whichensures the elimination of cells that have completed their life cycle or, upon genetic damage, have become useless or harmful for the organism. Because cells undergoing apoptosis carry out their own demise by activation of an internally encoded self-destruction program, apoptotic death represents a form of cell suicide. In recent years, the essential contribution of apoptosis to all stages of thelife of a multicellular organism, including development and growth, homeostasis during adulthood, and aging, has been widely accepted and intensively studied.3,4 Besides participation in physiologic processes, apoptotic mechanisms are also involved in the pathogenesis of a broad spectrum of diseases, including cancer, AIDS, and autoimmune conditions.3,4 The recognition of the significance ofapoptosis in health and disease has fueled extensive research efforts aimed at elucidation of the molecular mechanisms of apoptosis and application of this knowledge for the discovery of new therapeutic regimens. The present review is an attempt to summarize our current knowledge of the basic biologic aspects of apoptosis and to present the diseases of the oral and maxillofacial region that are...
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