Nuclear Receptors as Orchestrators of Regulatory Cell Death

Recently, a growing number of novel types of regulated cell death have been reported, including pyroptosis, necroptosis, and ferroptosis, among others. These types of cell death play crucial roles in a wide array of physiological functions such as metabolism, tissue injury and repair, chronic disease progression, and immune protection. However, specifically targeting cell death pathways for therapeutic purposes remains a challenge due to the unresolved complexities in pharmacological intervention. Nuclear receptor superfamily members, a class of prominent targets in drug discovery, are involved in diverse physiological and pathological processes. Investigating the regulatory functions between nuclear receptors and cell death is essential for understanding their roles in cell death and developing novel treatment methods for cell death-related diseases. This review discusses the mechanisms and functional significance of nuclear receptors in cell death across various physiological and pathological conditions, summarizes current ligands and compounds that facilitate targeting nuclear receptors to modulate cell death, and aims to promote the development of novel pharmacological strategies.