The Role of Pyroptosis in Alzheimer's Disease

Pyroptosis is a type of regulated cell death that relies on caspases, vesicles, and the cleavage of gasdermin proteins (which create pores in the cell membrane). The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, which is involved in this process, is the most widely studied inflammasome. Caspase-1 activates pro-inflammatory cytokines, such as IL-1 beta and IL-18. Gasdermin D (GSDMD) is the most important executive protein. GSDMD, a substrate rather than an upstream protease, determines the occurrence of pyroptosis. Pyroptosis is essential for maintaining body homeostasis, but excessive or poorly regulated cell death can aggravate the inflammatory response. Undoubtedly, this will be an important direction for future research on Alzheimer's disease (AD). Here, we review recent research progress on the morphological characteristics, molecular mechanisms, and role of pyroptosis in the context of AD, thereby providing new directions for identifying potential disease biomarkers and treatment strategies for AD.