Apoptosis: An Overview of the Process and Its Relevance in Disease

Abstract

Publisher Summary This chapter provides an overview of several recent advances in the study of apoptosis, integrating the molecular events with the physiological and pathophysiological significance of this process. Apoptosis is an evolutionarily conserved, innate process by which cells systematically inactivate, disassemble, and degrade their own structural and functional components to complete their own demise. It can be activated intracellularly through a genetically defined developmental program or extracellularly by endogenous proteins, cytokines, and hormones, as well as xenobiotic compounds, radiation, oxidative stress, and hypoxia. The ability of a cell to undergo apoptosis in response to a death signal is related to its proliferative status, cell cycle position, and the controlled expression of genes that promote, inhibit, and affect the death program. Dysregulated apoptosis, resulting in excessive, untimely, or insufficient cell death, is fundamental to the initiation and progression of many human diseases. Increased neuronal cell apoptosis is thought to contribute to the progression and severity of several neurodegenerative disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, Parkinson's disease, motor neuron disease, and even stroke. Excessive apoptosis of circulating T cells is correlated with severe immunodeficiency syndrome and AIDS, whereas insufficient apoptosis is a mechanism for certain autoimmune and lymphoproliferative disorders. A lot of research on the biochemical and genetic mechanisms involved in apoptosis has begun to provide with an appreciation of the complexity of the triggers and effector pathways that mediate this fundamental process.