Induction Mechanism of Ferroptosis, Necroptosis, and Pyroptosis: A Novel Therapeutic Target in Nervous System Diseases

In recent years, three emerging cell deaths, ferroptosis, necroptosis and pyroptosis, have gradually attracted everyone's attention, and they also play an important role in the occurrence and development of various diseases. Ferroptosis is an idiographic iron-dependent form regulated cell death with the hallmark of accumulation of the intracellular reactive oxygen species (ROS). Necroptosis is a form of regulated necrotic cell death mediated by the receptor-interacting protein kinase 1(RIPK1) and receptor-interacting protein kinase 3RIPK3. Pyroptosis, also known as cell inflammatory necrosis, is a programmed cell necrosis mediated by Gasdermin D (GSDMD). It is manifested by the continuous swelling of the cells until the cell membrane ruptures, resulting in the release of the cell contents and the activation of a strong inflammatory response. Neurological disorders remain a clinical challenge and patients do not respond well to conventional treatments. Nerve cell death can aggravate the occurrence and development of neurological diseases. This article reviews the specific mechanisms of these three types of cell death and their relationship with neurological diseases and the evidence for the role of the three types of cell death in neurological diseases; understanding these pathways and their mechanisms is helpful for the treatment of neurological diseases.

Automated summary

In recent years, the emerging cell deaths of ferroptosis, necroptosis, and pyroptosis have attracted attention for their roles in various diseases. Ferroptosis is an iron-dependent form of cell death characterized by accumulation of reactive oxygen species (ROS). Necroptosis is a regulated necrotic cell death mediated by RIPK1 and RIPK3. Pyroptosis, or cell inflammatory necrosis, is a programmed cell death mediated by GSDMD. This article provides a review of the specific mechanisms of these cell deaths, their relationship with neurological diseases, and the evidence for their role in these diseases.