Cross-talk between pyroptosis and miRNAs in Alzheimer disease neuropathology, therapeutic targeting of NLRP inflammasomes, and recent advances in nanoparticle-targeted therapy.

Alzheimer disease (AD) is a widespread neurodegenerative disorder. It is pathologically marked by the deposition of β-amyloid (Aβ) plaques and a high phosphorylation level of tau proteins, resulting in neurofibrillary tangle development, cognitive decline, and neuronal loss. Previous studies showed the correlation between AD and pyroptosis, an inflammasome-mediated programmed cell death. It was reported that Aβ and tau deposits may activate the NOD-like receptor pyrin domain-3 (NLRP3) and inflammasome-caspase-1-gasdermin D (GSDMD) pathway. This leads to cell membrane rupture and discharge of IL-1β and IL-18 cytokines that initiate neuroinflammation. However, there is still a lack of research on therapeutic approaches that target the pyroptotic pathway in AD. This review documents recent research on the regulatory function of miRNAs in regulating the NLRP3/caspase-1/GSDMD pathways and their potential to lessen pyroptosis-induced neuronal damage. We also address novel platforms for delivering antipyroptotic drugs and miRNA modulators across the blood-brain barrier using nanotechnology, such as engineered nanocarriers and exosome-like nanoparticles. These approaches have a promising therapeutic implication as potential treatment options for AD by combining molecular regulation and nanomedicine.