Inhibitors of Apoptosis Proteins as Potential Research Targets for Decoding the Pathological Mechanisms of Autoimmune Diseases

Abstract

Necroptosis, a type of pathological and inflammatory cell death, resembles necrosis, the termination of function of a bodily tissue, but adopts a unique molecular pathway that is not like apoptosis, resulting in vastly different immunological consequences. Until recently, necroptosis was believed to mainly function as a protective mechanism that counteracts the viral barrier of apoptosis. However, mouse model studies have indicated that deficiency in elements of the apoptosis machinery such as caspase-8 or FADD can result in embryonic lethality driven by necroptosis. Previous studies using conditional depletion of cellular inhibitors of apoptosis (cIAPs) revealed that the necroptosis pathway is triggered under certain stressor conditions. These data support a new approach of targeting molecules within the cell death pathways to identify the origin of autoimmune diseases. Hence, distinguishing between these two types of cell death may prove crucial during pathologic evaluations. This review provides a detailed insight into the emerging discussion on the various forms of cell death and the essential roles which certain molecules play in the development and progression of autoimmune diseases. Armed with this knowledge, greater efforts can be targeted towards devising more effective treatments for interception of pathological diseases, prior to their uncontrollable progression.