Programmed Cell Death Mechanisms in Neurological Disease

Dale   E.   Bredesen

Abstract

Programmed cell death (pcd) is a form of cell death in which the cell plays an active role in its own demise. Pcd plays a critical role in the development of the nervous system, as well as in its response to insult. Both anti-pcd and pro-pcd modulators play prominent roles in development and disease, including neurodegeneration, cancer, and ischemic vascular disease, among others. Over 100,000 published studies on one form of programmed cell death — apoptosis — have appeared, but recent studies from multiple laboratories suggest the existence of non-apoptotic forms of programmed cell death, such as autophagic programmed cell death. In addition, there appear to be programmatic cell deaths that do not fit the criteria for either apoptosis or autophagic cell death, arguing that additional programs may also be available to cells. Constructing a mechanistic taxonomy of all forms of pcd — based on inhibitors, activators, and identified biochemical pathways involved in each form of pcd — should offer new insight into cell deaths associated with various disease states, and ultimately offer new therapeutic approaches.

Keywords: Programmed cell death, autophagy, caspase, apoptosis, paraptosis, dependence receptors, neurodegeneration, Alzheimer's disease