Suicide cells in normal and pathological

Abstract

Introduction: The cells of a multicellular organism are members of a highly organized community. The number of cells in this community is highly regulated — not simply by controlling the rate of cell division, but also by controlling the rate of cell death. If cells are no longer needed, they commit suicide by activating an intracellular death program. This process is called programmed cell death, or apoptosis (from a Greek word meaning “falling off,” as leaves from a tree). Apoptosis is a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. The purpose of this review is to provide a general overview of current knowledge on the process of apoptosis, the role of apoptosis in health and disease, as well as a discussion of potential alternative forms of apoptosis. The mechanisms of apoptosis are highly complex, involving an energy-dependent cascade of molecular events. Recent studies indicate that there are two main apoptotic pathways: the extrinsic and the intrinsic. There is an additional pathway, that involves T-cell mediated cytotoxicity and perforin-granzyme-dependent killing of the cell. The perforin/granzyme pathway can induce apoptosis via either granzyme B or granzyme A. The extrinsic, intrinsic, and granzyme B pathways converge to the same final, or execution pathway. This pathway is initiated by the cleavage of caspase-3 and results in DNA fragmentation, degradation of cytoskeletal and nuclear proteins, cross-linking of proteins, formation of apoptotic bodies, expression of ligands for phagocytic cell receptors and finally uptake by phagocytic cells. Abnormalities in cell death regulation can be a significant component of diseases such as cancer, autoimmune lymphoproliferative syndrome, AIDS, ischemia, and neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and Amyotrophic Lateral Sclerosis. Some conditions feature insufficient apoptosis whereas others feature excessive apoptosis. Conclusions: Apoptosis is a highly regulated energy-dependent process. The importance of apoptosis consists in understanding its mechanism, because it is a vital component of health maintenance and disease outbreak. The widespread involvement of apoptosis in the pathophysiology of disease define studying the treatment strategies of that disease. Understanding the mechanisms of apoptosis at the molecular level provides deeper insight into various disease processes and may thus influence therapeutic strategy.